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Hydraulic actuated quadruped robots have bright application prospects and significant research values in unmanned area investigation, disaster rescue and other scenarios, due to the advantages of high payload and high power to weight ratio. Among these fields, inevitable collision of robots may occur when contact with unknown objects, step on empty objects, or collapse, all of which have an impact on the working hydraulic system. To overcome the unknown external disturbances, this paper proposes an active disturbance rejection control (ADRC) strategy of double vane hydraulic rotary actuators for the hip joints of the quadruped robots. Considering the order of the valve-controlled actuator model, a three-stage tracking differentiator, a four-stage extended state observer, and a state error feedback controller are designed relatively, and the extended state observer is adopted to observe and compensate the uncertainty of external load torque of the system. The effectiveness of the ADRC method is verified in simulation environment and a single joint experimental platform. Moreover, the impact experiments of the limb leg unit are carried out after introducing the proposed ADRC strategy into hip joint, the limb leg unit of quadruped robots presents better impact resistance ability. [ABSTRACT FROM AUTHOR]

High-end equipment always operate in low-speed and heavy-load working environments, highlighting the need for cam-lobe hydraulic motors with excellent speed stability (< 1 r/min) and ultrahigh-power rotary output (> 1 MW). The successful operation of cam-lobe hydraulic motors relies on the circulation supply of high- and low-pressure oil. However, the switching between high-/low-pressure oil controlled by the oil distributor inevitably causes an obvious pressure impact and speed pulsation, which directly reduces the speed stability of hydraulic motors. Therefore, an optimization design approach for the oil distributor port is proposed to minimize the speed pulsation of cam-lobe hydraulic motors. In the proposed approach, a simulation model that links the oil distributor port structural parameters with the hydraulic motor speed pulsation was developed to clarify the effect of the oil distributor structural parameters on speed pulsation. Then, an orthogonal analysis method was used to identify the optimized oil distributor port structural parameters while minimizing the hydraulic motor's speed pulsation as much as possible. Finally, several experiments were conducted to validate the effectiveness and accuracy of the proposed optimization design approach. The experimental results indicate that the pulsation rate of the hydraulic motor equipped with the optimized oil distributor was 62.5% lower than that of the original motor at a working pressure of 25 MPa, which is consistent with the simulation results using the proposed optimization design approach. The findings of this study offer a feasible and effective approach to guide the design optimization of the oil distributor port for low-pulsation hydraulic motors. [ABSTRACT FROM AUTHOR]

Cam-lobe radial-piston hydraulic motors are widely used as rotation driving units for various marine machinery owing to their ultrahigh output torque (more than 100 kN m). A multi-row cam roller bearing (MCRB) is the key component that directly determines the fatigue life of a cam-lobe radial-piston hydraulic motor. However, compact geometry and complex loads render MCRB susceptible to fatigue failure, highlighting the need for an optimized MCRB to achieve longer fatigue life and higher reliability. Therefore, this study proposes an innovative geometry optimization method for an MCRB to improve its fatigue life. In this method, a quasi-static model was developed to calculate the load distribution, with the fatigue life of the MCRB calculated using both basic dynamic loading and load distribution. Subsequently, a genetic algorithm was used to obtain the optimized geometry parameters, which significantly improved the fatigue life of the MCRB. Finally, a loading test was conducted on a hydraulic motor installed with both the initial and optimized MCRB to validate the effectiveness of the proposed optimization method. This study provides a theoretical guideline for optimizing the design of MCRB, thereby increasing the fatigue life of hydraulic motors. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive type of B-cell lymphoma. Unfortunately, about one-third of patients either relapse after the initial treatment or are refractory to first-line therapy, indicating a need for new treatment modalities. PIM serine/threonine kinases are proteins that are associated with genetic mutations, overexpression, or translocation events in B-cell lymphomas. We conducted an integrative analysis of whole-exome sequencing in 52 DLBCL patients, and no amplification, mutation, or translocation of the PIM1 gene was detected. Instead, analyses of TCGA and GTEx databases identified that PIM1 expression was increased in DLBCL samples compared to normal tissue, and high expression levels were associated with poor overall survival. Moreover, interference of PIM1 significantly suppressed DLBCL cell proliferation. In addition, we identified anwulignan, a natural small-molecule compound, as a PIM1 inhibitor. Anwulignan directly binds to PIM1 and exerts antitumor effects on DLBCL in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, we identified an effective synergistic combination between anwulignan and chidamide. Our findings suggested that PIM1 could be a therapeutic target and prognostic factor for DLBCL, and anwulignan holds promise for future development as a natural product for treatment. [ABSTRACT FROM AUTHOR]

In recent years, cat-state encoding and high-dimensional entanglement have attracted much attention. However, previous works are limited to generation of entangled states of cat-state qubits (two-dimensional entanglement with cat-state encoding), while how to prepare entangled states of cat-state qutrits or qudits (high-dimensional entanglement with cat-state encoding) has not been investigated. We here propose to generate a maximally-entangled state of multiple cat-state qutrits (three-dimensional entanglement by cat-state encoding) in circuit QED. The entangled state is prepared with multiple microwave cavities coupled to a superconducting flux ququart (a four-level quantum system). This proposal operates essentially by the cavity-qutrit dispersive interaction. The circuit hardware resource is minimized because only a coupler ququart is employed. The higher intermediate level of the ququart is occupied only for a short time, thereby decoherence from this level is greatly suppressed during the state preparation. Remarkably, the state preparation time does not depend on the number of the qutrits, thus it does not increase with the number of the qutrits. As an example, our numerical simulations demonstrate that, with the present circuit QED technology, the high-fidelity preparation is feasible for a maximally-entangled state of two cat-state qutrits. Furthermore, we numerically analyze the effect of the inter-cavity crosstalk on the scalability of this proposal. This proposal is universal and can be extended to accomplish the same task with multiple microwave or optical cavities coupled to a natural or artificial four-level atom. [ABSTRACT FROM AUTHOR]

Marine umbilical is one of the key equipment for subsea oil and gas exploitation, which is usually integrated by a great number of different functional components with multi-layers. The layout of these components directly affects manufacturing, operation and storage performances of the umbilical. For the multi-layer cross-sectional layout design of the umbilical, a quantifiable multi-objective optimization model is established according to the operation and storage requirements. Considering the manufacturing factors, the multi-layering strategy based on contact point identification is introduced for a great number of functional components. Then, the GA-GLM global optimization algorithm is proposed combining the genetic algorithm and the generalized multiplier method, and the selection operator of the genetic algorithm is improved based on the steepest descent method. Genetic algorithm is used to find the optimal solution in the global space, which can converge from any initial layout to the feasible layout solution. The feasible layout solution is taken as the initial value of the generalized multiplier method for fast and accurate solution. Finally, taking umbilicals with a great number of components as examples, the results show that the cross-sectional performance of the umbilical obtained by optimization algorithm is better and the solution efficiency is higher. Meanwhile, the multi-layering strategy is effective and feasible. The design method proposed in this paper can quickly obtain the optimal multi-layer cross-sectional layout, which replaces the manual design, and provides useful reference and guidance for the umbilical industry. [ABSTRACT FROM AUTHOR]

Quantitative cultural studies have witnessed a surge with the rapid development of computer technology in recent years. Since ancient literature constitutes a long-time-span repository for human culture, with quantitative methods and ancient texts, scholars can study the genesis and progression of human history and society across historical epochs from digital perspectives. Nevertheless, traditional humanities scholars often lack the requisite technical skills, creating a demand for interactive platforms. This paper introduces the Evol platform—an online tool designed for the quantitative analysis of ancient literature. Equipped with various analysis functions and visualization tools, the Evol platform allows users to quantify literary documents through intuitive online interaction. Using this platform, we investigated three cases of cultural evolution in ancient Chinese history: (1) the changing attitude of the government towards nomadic ethnic groups; (2) the formulation and propagation of an allusion phrase related to the Battle of Muye; (3) the influence of the Book of Changes across diverse cultural domains. By showcasing cases across diverse semantic units and topics, Evol demonstrates its potential in providing efficient and low-cost experimental tools catering to the realms of culturomics, history, and philology. [ABSTRACT FROM AUTHOR]

The W-type entangled states are very useful in quantum computing and quantum communication. Many works have been devoted to preparing non-hybrid W states (i.e., all qubits with the same encoding) in various physical systems. On the other hand, hybrid W entangled states are key ingredients for hybrid quantum computing and quantum communication. In this work, we propose to create a hybrid W entangled state of three photonic qubits each with a different encoding. The hybrid W state is prepared by employing three microwave cavities coupled to a superconducting flux qutrit (i.e., a three-level quantum system). This proposal requires only a single qutrit to couple the three cavities, thus the system architecture is greatly simplified. Since there is no need of making any measurement, the W state is created deterministically. As an example, our numerical simulation demonstrates that within current experimental technology, the proposed hybrid W state can be created with a high fidelity. This proposal is universal and can be applied to create the proposed hybrid W state, by using three microwave or optical cavities coupled to a three-level natural or artificial atom. [ABSTRACT FROM AUTHOR]

Motivated by recent realizations of two-dimensional (2D) superconducting-qubit lattices, we propose a protocol to simulate Hofstadter butterfly with synthetic gauge fields in superconducting circuits. Based on the existing 2D superconducting-qubit lattices, we construct a generalized Hofstadter model on zigzag lattices, which has a fractal energy spectrum similar to the original Hofstadter butterfly. By periodically modulating the resonant frequencies of qubits, we engineer a synthetic gauge field to mimic the generalized Hofstadter Hamiltonian. A spectroscopic method is used to demonstrate the Hofstadter butterfly from the time evolutions of experimental observables. We numerically simulate the dynamics of the system with realistic parameters, and the results show a butterfly spectrum clearly. Our proposal provides a promising way to realize the Hofstadter butterfly on the latest 2D superconducting-qubit lattices and will stimulate the quantum simulation of novel properties induced by magnetic fields in superconducting circuits. [ABSTRACT FROM AUTHOR]

Human social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions. Many real-world systems are characterized by bursty dynamics with interchanging periods of intense activity and quiescence. The authors propose a method to construct temporal networks that match a given activity pattern, and apply it to empirical bursty patterns. [ABSTRACT FROM AUTHOR]

The widespread contamination of the environment by polyhalogenated carbazoles (PHCZs) has been increasingly observed during the past decade. Among numerous PHCZ congeners, 3,6-dichlorocarbazole (36-CCZ) is often among the most frequently detected at higher concentrations. Although the environmental level of the legacy pesticide p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) has been declining, it continues to be ubiquitously detected. These two compounds were found to interfere with each other during analyses using gas chromatography (GC) coupled with single- or triple-quadrupole low-resolution mass spectrometry (MS or MS/MS). The base peak in the mass spectra was that of m/z 235 for both compounds. In MS/MS with multiple reaction monitoring (MRM), the same transitions (235 → 200 and 235 → 165) were often used. Under the same GC operating conditions, the SH-I-5MS capillary column used in this work did not resolve the two compounds at baseline. Pre-treatment using cleanup column chromatography can fractionate the sample extract, with the two compounds separated in different fractions before instrumental analyses. Reversed-phase HPLC columns also work for resolving 36-CCZ and p,p′-DDT. Possible overlaps in GC retention and similarity in MS spectra might have caused data inaccuracy for 36-CCZ as well as p,p′-DDT in some studies published to date, and steps to avoid the interference should be taken into quality control protocols in future research and environmental monitoring. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. Methods: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398). Results: Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4–34.0) than among those who received none (16.1 months, 95%CI 12.9–19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35–0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17–0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. Conclusions: ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection. [ABSTRACT FROM AUTHOR]

A precise analytical method based on QuEChERS has been proposed for the concurrent determination of 11 polyhalogenated carbazoles (PHCZs), benzocarbazole (BZCZ), and 9H-carbazoles (CZ). The quantification was confirmed by gas chromatography using triple quadrupole tandem mass spectrometry (Shimadzu GC–MS/MS-TQ8040) and gas chromatography coupled mass spectrometry (Agilent 7890A-5973 GC–MS). The developed method was validated by testing the following parameters: linearity, instrument limit of detection (LOD), instrument limit of quantification (LOQ), method limit of detection (MLD), method limit of quantification (MLQ), matrix effect (ME), accuracy, and precision. All compounds showed good linearity in the range of 0.005–0.2 μg/mL with correlation coefficients higher than 0.992. The method demonstrated satisfactory recoveries (ranging from 71.21 to 105.04%) for most of the compounds with relative standard deviation precision (RSD) < 10.46%, except 3-BCZ (Recovery = 67.53%, RSD = 2.83%). The values of LOD and LOQ varied from 0.05 to 0.24 ng and 0.14 to 0.92 ng, respectively, while those of MLD and MLQ ranged from 0.02 to 0.12 ng/g wet weight (ww) and 0.07 to 0.45 ng/g ww, respectively. The developed method represents a reliable tool for the routine analysis of PHCZ congeners in invertebrate animals. [ABSTRACT FROM AUTHOR]

Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young's moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa—over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices. Stretchable electronics are attractive for a range of biomedical applications, but are challenging to prepare with suitable mechanical properties. Here, the authors report the use of a soft interlayer that allows the development of stretchable electronics with tissue-like material properties. [ABSTRACT FROM AUTHOR]

Being recognized among the cradles of human civilization, ancient China nurtured the longest continuous academic traditions and humanistic spirits, which continue to impact today’s society. With an unprecedented large-scale corpus spanning 3000 years, this paper presents a quantitative analysis of cultural evolution in ancient China. Millions of intertextual associations are identified and modelled with a hierarchical framework via deep neural network and graph computation, thus allowing us to answer three progressive questions quantitatively: (1) What is the interaction between individual scholars and philosophical schools? (2) What are the vicissitudes of schools in ancient Chinese history? (3) How did ancient China develop a cross-cultural exchange with an externally introduced religion such as Buddhism? The results suggest that the proposed hierarchical framework for intertextuality modelling can provide sound suggestions for large-scale quantitative studies of ancient literature. An online platform is developed for custom data analysis within this corpus, which encourages researchers and enthusiasts to gain insight into this work. This interdisciplinary study inspires the re-understanding of ancient Chinese culture from a digital humanities perspective and prompts the collaboration between humanities and computer science. [ABSTRACT FROM AUTHOR]

Ecological poverty alleviation (EPA) is an effective strategy to address the vicious circle of poverty and environmental destruction in poor areas. However, it remains controversial whether this strategy has really succeeded in this respect. Previous research investigated the impact of a certain factor on EPA, and only few studies integrated them to explore their differential effects, thereby overlooking the complexity of EPA. Therefore, this study quantified the overall efficiency of the EPA strategies of 28 poor counties in three provinces of Northeast China from 2005 to 2018 by using a super-efficiency slacks-based measure model. This model can take into account undesirable outputs; as such, it has significant advantages in measuring the coordination among economic and social development and environmental protection. The Tobit model was used to explore the factors influencing EPA efficiency. The results show that, first, the majority of counties investigated had an EPA efficiency below the overall national average. Second, as for the factors influencing EPA efficiency, it was found that (1) GDP per capita and investment in environmental governance favored EPA efficiency, as they are conducive to stimulating regional consumption dynamics and achieving green economic development; (2) science and technology expenditure and urbanization were not conducive to EPA efficiency; and (3) industrial structure and trade had insignificant effects on EPA efficiency, due to the small scale of industry and the inadequacy of the policy system. This study assessed EPA efficiency from a holistic perspective, and addressed the controversies over EPA's influencing factors, thereby providing an effective method to conduct regional EPA assessment and improve EPA performance in poor regions of China. [ABSTRACT FROM AUTHOR]

Uncertainty relations are of profound significance in quantum mechanics and quantum information theory. The well-known Heisenberg-Robertson uncertainty relation presents the constraints on the spread of measurement outcomes caused by the non-commutability of a pair of observables. In this article, we study the uncertainty relation of triple observables to explore the relationship between the standard deviations and the commutators of the observables. We derive and tighten the multiplicative form and weighted summation form uncertainty relations, which are found to be dependent not only on the commutation relations of each pair of the observables but also on a newly defined commutator in terms of all the three observables. We experimentally test the uncertainty relations in a linear optical setup. The experimental and numerical results agree well and show that the uncertainty relations derived by us successfully present tight lower bounds in the cases of high-dimensional observables and the cases of mixed states. Our method of deriving the uncertainty relation can be extended to more than three observables. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of alternative splicing (AS) triggers many tumours, understanding the roles of splicing events during tumorigenesis would open new avenues for therapies and prognosis in multiple myeloma (MM). Methods: Molecular, genetic, bioinformatic and statistic approaches are used to determine the mechanism of the candidate splicing factor (SF) in myeloma cell lines, myeloma xenograft models and MM patient samples. Results: GSEA reveals a significant difference in the expression pattern of the alternative splicing pathway genes, notably enriched in MM patients. Upregulation of the splicing factor SRSF1 is observed in the progression of plasma cell dyscrasias and predicts MM patients' poor prognosis. The c-indices of the Cox model indicated that SRSF1 improved the prognostic stratification of MM patients. Moreover, SRSF1 knockdown exerts a broad anti-myeloma activity in vitro and in vivo. The upregulation of SRSF1 is caused by the transcription factor YY1, which also functions as an oncogene in myeloma cells. Through RNA-Seq, we systematically verify that SRSF1 promotes the tumorigenesis of myeloma cells by switching AS events. Conclusion: Our results emphasise the importance of AS for promoting tumorigenesis of MM. The candidate SF might be considered as a valuable therapeutic target and a potential prognostic biomarker for MM. [ABSTRACT FROM AUTHOR]

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia–reperfusion injury, the cause of brain and spinal cord ischemia–reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia–reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia–reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition. [ABSTRACT FROM AUTHOR]

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A series of new systems of the SrCe1-xTixO3 and SrCe1−xZrxO3 (SCTx and SCZx, x = 0.0–0.1) ceramics have been prepared by the traditional solid-phase methods. The XRD patterns results show that an ABO3-type perovskite structure of the SrCeO3 ceramic can be obtained as x = 0.0. With the increase in Ti4+- and Zr4+-ions-doping content of x = 0.02–0.1, the SCTx and SCZx ceramics basically belong to the perovskite phase with the orthorhombic structure of the space group Pmcn (62), and the results of EDS analysis on the proportion of each element can also verify the correctness of the XRD analytical results. In addition, all the microstructures are dense for the SCTx and SCZx (x = 0.0–0.1) samples. The fitting results of complex plane impedance verified that the temperature stability of SCTx solid solution ceramics is more suitable for adjusting to the practical application range. Especially, the SCTx (x = 0.03) ceramics sintered at 1270 °C for 4 h can obtain the relatively excellent dielectric properties of εr = 50.16, Q × f = 8,940 GHz (at 5.91 GHz), and τf = + 0.08 ppm/°C. [ABSTRACT FROM AUTHOR]

Well-designed surface textures can improve the tribological properties and the efficiency of the electrohydrostatic actuator (EHA) pump under high-speed and high-pressure conditions. This study proposes a multi-objective optimization model to obtain the arbitrarily surface textures design of the slipper/swash plate interface for improving the mechanical and volumetric efficiency of the EHA pump. The model is composed of the lubrication film model, the component dynamic model considering the spinning motion, and the multi-objective optimization model. In this way, the arbitrary-shaped surface texture with the best comprehensive effect in the EHA pump is achieved and its positive effects in the EHA pump prototype are verified. Experimental results show a reduction in wear and an improvement in mechanical and volumetric efficiency by 1.4% and 0.8%, respectively, with the textured swash plate compared with the untextured one. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a highly malignant tumor with a poor prognosis. Hypoxia conditions affect multiple cellular processes promoting the adaptation and progression of cancer cells via the activation of hypoxia-inducible factors (HIF) and subsequent transcription activation of their target genes. Preliminary studies have suggested that estrogen receptor β (ERβ) might play a promoting role in the progression of NSCLC. However, the precise mechanisms, particularly its connection to HIF-1α-mediated modulation under hypoxia, remain unclear. Our findings demonstrated that the overexpression of ERβ, not ERα, increased cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts. Tissue microarray staining revealed a strong correlation between the protein expression of HIF-1α and ERβ. HIF-1α induced ERβ gene transcription and protein expression in CoCl2-induced hypoxia, 1% O2 incubation, or HIF-1α overexpressing cells. ChIP identified HIF-1α binding to a hypoxia response element in the ESR2 promoter. The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the tumor growth, thus emphasizing the promising prospects of targeting HIF-1α and ERβ as a therapeutic approach for the treatment of NSCLC.ERβ, not ERα, increases cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts.A strong correlation exists between the protein expression of HIF-1α and ERβ.HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter.The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth.ERβ, not ERα, increases cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts.A strong correlation exists between the protein expression of HIF-1α and ERβ.HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter.The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth.Key messages: Non-small cell lung cancer (NSCLC) is a highly malignant tumor with a poor prognosis. Hypoxia conditions affect multiple cellular processes promoting the adaptation and progression of cancer cells via the activation of hypoxia-inducible factors (HIF) and subsequent transcription activation of their target genes. Preliminary studies have suggested that estrogen receptor β (ERβ) might play a promoting role in the progression of NSCLC. However, the precise mechanisms, particularly its connection to HIF-1α-mediated modulation under hypoxia, remain unclear. Our findings demonstrated that the overexpression of ERβ, not ERα, increased cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts. Tissue microarray staining revealed a strong correlation between the protein expression of HIF-1α and ERβ. HIF-1α induced ERβ gene transcription and protein expression in CoCl2-induced hypoxia, 1% O2 incubation, or HIF-1α overexpressing cells. ChIP identified HIF-1α binding to a hypoxia response element in the ESR2 promoter. The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the tumor growth, thus emphasizing the promising prospects of targeting HIF-1α and ERβ as a therapeutic approach for the treatment of NSCLC.ERβ, not ERα, increases cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts.A strong correlation exists between the protein expression of HIF-1α and ERβ.HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter.The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth.ERβ, not ERα, increases cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts.A strong correlation exists between the protein expression of HIF-1α and ERβ.HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter.The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth. [ABSTRACT FROM AUTHOR]

Our knowledge of the role of the gut microbiome in acute coronavirus disease 2019 (COVID-19) and post-acute COVID-19 is rapidly increasing, whereas little is known regarding the contribution of multi-kingdom microbiota and host-microbial interactions to COVID-19 severity and consequences. Herein, we perform an integrated analysis using 296 fecal metagenomes, 79 fecal metabolomics, viral load in 1378 respiratory tract samples, and clinical features of 133 COVID-19 patients prospectively followed for up to 6 months. Metagenomic-based clustering identifies two robust ecological clusters (hereafter referred to as Clusters 1 and 2), of which Cluster 1 is significantly associated with severe COVID-19 and the development of post-acute COVID-19 syndrome. Significant differences between clusters could be explained by both multi-kingdom ecological drivers (bacteria, fungi, and viruses) and host factors with a good predictive value and an area under the curve (AUC) of 0.98. A model combining host and microbial factors could predict the duration of respiratory viral shedding with 82.1% accuracy (error ± 3 days). These results highlight the potential utility of host phenotype and multi-kingdom microbiota profiling as a prognostic tool for patients with COVID-19. Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91–0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87–0.93) at a specificity of 0.76 to 0.98 (IQR 0.83–0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79–0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration. Here, using fecal metagenomics data of 2,320 individuals, the authors develop a microbiome-based machine learning approach showing high accuracy for multi-class disease diagnosis, highlighting its potential application in improving noninvasive diagnostics and monitor responses to therapy. [ABSTRACT FROM AUTHOR]

As a new form of plastic deformation, ultrasonic vibration-assisted deformation has recently attracted extensive attention, while its microstructure evolution and mechanical response remain unclear. In this paper, a gradient grain/twin structure of CrCoNi medium entropy alloy (MEA) was constructed by performing ultrasonic vibration surface friction treatment (UV-SFT) to improve its mechanical properties. Before and after plastic deformation, such a constructed microstructure was characterized by using an optical microscope, scanning electron microscope, electron backscattered diffraction, and transmission electron microscope, and thus both the microhardness and uniaxial tensile testing were performed. After the CrCoNi MEA has been experimentally treated with a UV-SFT process, not only does it exhibit a gradient grain/twin structure but the gradient deformation layer can also be divided into three parts: (1) the main features closest to the outer layer are nanocrystals and twins bent by deformation; (2) the severely plastic deformed layer leads to elongated lamellar grains and crossed multi-twinning systems; and (3) the transition layer mainly presents parallel twins and dislocation movements. Ultrasonic vibration surface plastic deformation significantly improves the yield strength and ultimate tensile strength of the CrCoNi MEA without loss of its plasticity, and shows excellent mechanical properties. [ABSTRACT FROM AUTHOR]

Cotton aphid (Aphis gossypii Glover) is regarded as one of the most harmful insect pests for cotton production. They are usually capable of causing severe yield loss through sucking plant sap, secreting honeydew and transmitting plant viral diseases. However, the molecular mechanism of the interaction between cotton and cotton aphids remains unclear currently. Therefore, the RNA-Seq study of cotton leaves was performed in response to cotton aphid damage at different time points (0 h, 6 h, 12 h, 24 h, 48 h and 72 h). A total of 9, 103 new genes were identified, and 7, 510 of them were annotated functionally. Based on the comparison results, the gene expression was analyzed according to the expression amount of genes in different samples. 24,793 differentially expressed genes (DEGs) were authenticated in all and their functional annotation and enrichment analysis were conducted. Compared with 0 h (without aphid damage, CK), the amount of down-regulated DEGs was largely more than that of the up-regulated DEGs at different time points under cotton aphid attack except for 48 h. As revealed by the functional annotation of DEGs, these genes are involved in all kinds of plant biological processes, including various resistance to abiotic and biotic stress, hormone metabolism, signaling transduction and transcriptional regulation. The results revealed the molecular mechanism of the interaction between cotton and cotton aphids and would facilitate the development of plant aphid-resistant cultivars. [ABSTRACT FROM AUTHOR]

We propose an efficient scheme to implement a multiplex-controlled phase gate with multiple photonic qubits simultaneously controlling one target photonic qubit based on circuit quantum electrodynamics (QED). For convenience, we denote this multiqubit gate as MCP gate. The gate is realized by using a two-level coupler to couple multiple cavities. The coupler here is a superconducting qubit. This scheme is simple because the gate implementation requires only one step of operation. In addition, this scheme is quite general because the two logic states of each photonic qubit can be encoded with a vacuum state and an arbitrary non-vacuum state ∣φ〉 (e.g., a Fock state, a superposition of Fock states, a cat state, or a coherent state, etc.) which is orthogonal or quasi-orthogonal to the vacuum state. The scheme has some additional advantages: because only two levels of the coupler are used, i.e., no auxiliary levels are utilized, decoherence from higher energy levels of the coupler is avoided; the gate operation time does not depend on the number of qubits; and the gate is implemented deterministically because no measurement is applied. As an example, we numerically analyze the circuit-QED based experimental feasibility of implementing a three-qubit MCP gate with photonic qubits each encoded via a vacuum state and a cat state. The scheme can be applied to accomplish the same task in a wide range of physical system, which consists of multiple microwave or optical cavities coupled to a two-level coupler such as a natural or artificial atom. [ABSTRACT FROM AUTHOR]

Hybrid entangled states are of fundamental interest in quantum physics and have significant applications in hybrid quantum communication and quantum computation. A great amount of work has been devoted to creating hybrid entangled states using two kinds of quantum systems or two types of qubits. Attention has been recently shifted to preparing hybrid entangled states with three kinds of quantum systems or three types of qubit encodings. Using three cavities coupled to a superconducting qutrit (i.e., a three-level quantum system), here we present a scheme to prepare a hybrid tripartite Greenberger–Horne–Zeilinger (GHZ) entangled state with three types of photonic qubits, each type containing one photonic qubit. By using a superconducting qutrit to couple three groups of cavities, we further show that the scheme can be generalized to create a hybrid multipartite GHZ entangled state with three types of photonic qubits, each type containing multiple photonic qubits. This scheme has the following features and advantages. The GHZ state preparation requires only a single step of operation. The hardware resources are greatly reduced since only one qutrit is needed to couple all cavities. The GHZ state is deterministically created because no measurement is required. The operational time required for the GHZ state preparation does not increase with the number of qubits. Moreover, during the GHZ state preparation, the coupler qutrit stays in the ground state and thus decoherence from the coupler qutrit is significantly suppressed. As an example, we further discuss the experimental feasibility of creating a hybrid tripartite GHZ state with three types of photonic qubits, each type containing one photonic qubit. This proposal is universal and can be extended to create the proposed hybrid GHZ state in a wide range of physical system, which consists of microwave or optical cavities coupled to a qutrit such as a three-level natural or artificial atom. [ABSTRACT FROM AUTHOR]

The gradual advances of offshore oil and gas exploitation and the development tendency of equipment integration have prompted the design of a new type of the high-current composite umbilical to meet development needs. In order to study the mechanical behavior of the high-current composite umbilical (HCCU) and provide design suggestions, a theoretical analysis framework of the tension-torsion coupled behavior of the spirally wound structure is proposed, which focuses more on the radial mechanical behavior. Then, by considering the mechanical and thermal conditions during the operation of HCCU, a semi-analytical method of the tension and torsion stiffness of the high-current composite umbilical considering the temperature effect is established. Furthermore, a practical case of HCCU is given, and the thermal effect on the radial and axial mechanical behaviors are analyzed. It is found that the thermal effect has a significant influence on the radial stiffness, and shows non-linear variation characteristics. Finally, the sensitivity analysis is carried out to study the influence of the design parameter on the stiffness of tension and torsion. The results indicated that the equivalent radial stiffness and helical angle have obvious effect on the tension-torsion coupled stiffness, which can provide reasonable reference for the design of HCCU. [ABSTRACT FROM AUTHOR]

In this study, a validated CFD model is used to analyze the flow field and pollutant distribution in an isolated canyon (street aspect ratio, W/H = 1) by considering different street categories and arrangements of void deck under a perpendicular inflow wind. The results reveal that the street geometry affects significantly the in-canyon flow structures and thus the pollutant distributions. Comparing with the regular street canyon (a main clockwise vortex is obtained therein), the void deck can cause several vortices when a strong stream of air passes through the canyon. It is the most conducive to pollutant removal for the void decks at both buildings, while the construction with void deck at the upstream building causes pollutant accumulation on the windward side. Moreover, a larger high-pollution zone is generated above the elevated road due to the wind recirculation therein, and for the two-level street and the street with depressed road, the weak wind leads to the accumulation of traffic pollutants in the underground space. This study will provide technical support for urban street planning and design to alleviate traffic pollution. [ABSTRACT FROM AUTHOR]

As a type of hydraulic rotary actuator, a helical hydraulic rotary actuator exhibits a large angle, high torque, and compact structure; hence, it has been widely used in various fields. However, its core technology is proprietary to several companies and thus has not been disclosed. Furthermore, the relevant reports are primarily limited to the component level. The dynamic characteristics of the output when a helical rotary actuator is applied to a closed-loop system are investigated from the perspective of driving system design. Two main aspects are considered: one is to establish a reliable mathematical model and the other is to consider the effect of system parameter perturbation on the output. In this study, a detailed mechanical analysis of a helical rotary hydraulic cylinder is first performed, factors such as friction and load are considered, and an accurate dynamic model of the actuator is established. Subsequently, considering the nonlinear characteristics of pressure flow and the dynamic characteristics of the valve, a dynamic model of a valve-controlled helical rotary actuator angle closed-loop system is described based on sixth-order nonlinear state equations, which has never been reported previously. After deriving the system model, a sensitivity analysis of 23 main parameters in the model with a perturbation of 10% is performed under nine operating conditions. Finally, the system dynamics model and sensitivity analysis results are verified via a prototype experiment and co-simulation, which demonstrate the reliability of the theoretical results obtained in this study. The results provide an accurate mathematical model and analysis basis for the structural optimization or control compensation of similar systems. [ABSTRACT FROM AUTHOR]

The corrosion behaviour and discharge performance of extruded Mg-xZn-1Ca (x = 0, 2, 5, 8) alloys, used as anodes for primary Mg-air batteries, were investigated by hydrogen evolution immersion, electrochemical and battery tests. The results show that the grain size first decreases and then increases with the increase Zn content. The type of the second phases changes from Mg2Ca to Ca2Mg6Zn3 and Ca2Mg5Zn13, and the percentage of the second phases increases. Among the four alloys, the ZX21 (Mg-2Zn-1Ca) alloy has the best corrosion and discharge performances, mainly uniform corrosion. The local corrosion of the other three alloys is mainly galvanic corrosion. At 10 mA cm−2, the anode efficiency, discharge capacity and discharge energy of the ZX21 alloy are 57.97%, 1244 mAhg−1 and 1493 mWhg−1, respectively. The improvement of the discharge performance of the ZX21 alloy is mainly due to the enrichment of Zn in the Mg2Ca phase, which reduces the potential difference between the matrix and Mg2Ca. It improves the corrosion performance of the alloy. In addition, the influence of the chunk effect diminished due to grain refinement. [ABSTRACT FROM AUTHOR]

Background: Female breast cancer has become the most commonly diagnosed cancer worldwide. As a tumor suppressor, estrogen receptor β (ERβ) can be potentially targeted for breast cancer therapy. Methods and results: TAD1822-7 was evaluated for ERβ-mediated autophagy and cell death using cell proliferation assay, Annexin V/PI staining, immunofluorescence, western blotting, ERβ siRNA, ERβ plasmid transfection and hypoxia cell models. TAD1822-7 upregulated ERβ causing cell death and induced mitochondrial dysfunction and autophagy companied with mitochondrial located ERβ. Enhanced levels of microtubule associated protein1 light chain 3 (LC3)-II and p62/SQSTM1 (p62) indicated that TAD1822-7 blocked the late-stage autolysosome formation, leading to cell death. Mechanistically, TAD1822-7-induced cell death was mediated by phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways. Moreover, TAD1822-7 modulated hypoxia inducible factor (HIF) functions and autophagy via the inhibition of HIF-1β in the context of hypoxia-induced autophagy. ERβ overexpression and ERβ agonist showed similar effects, whereas ERβ siRNA abrogated TAD1822-7-induced cell death, the inhibition of PI3K/AKT pathway and autophagy. The involvement of PI3K/AKT pathway and autophagy was also demonstrated in TAD1822-7-treated hypoxic breast cancer cells. Conclusions: These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin–proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. Key messages: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin–proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology. [ABSTRACT FROM AUTHOR]

We present a way to transfer maximally- or partially-entangled states of n single-photon-state (SPS) qubits onto n coherent-state (CS) qubits, by employing 2n microwave cavities coupled to a superconducting flux qutrit. The two logic states of a SPS qubit here are represented by the vacuum state and the single-photon state of a cavity, while the two logic states of a CS qubit are encoded with two coherent states of a cavity. Because of using only one superconducting qutrit as the coupler, the circuit architecture is significantly simplified. The operation time for the state transfer does not increase with the increasing of the number of qubits. When the dissipation of the system is negligible, the quantum state can be transferred in a deterministic way since no measurement is required. Furthermore, the higher-energy intermediate level of the coupler qutrit is not excited during the entire operation and thus decoherence from the qutrit is greatly suppressed. As a specific example, we numerically demonstrate that the high-fidelity transfer of a Bell state of two SPS qubits onto two CS qubits is achievable within the present-day circuit QED technology. Finally, it is worthy to note that when the dissipation is negligible, entangled states of n CS qubits can be transferred back onto n SPS qubits by performing reverse operations. This proposal is quite general and can be extended to accomplish the same task, by employing a natural or artificial atom to couple 2n microwave or optical cavities. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common tumor types globally. Despite the progress made in surgical procedures and therapeutic options, HCC remains a considerable cause of cancer-related mortality. In this study, we investigated the antitumor effects of sanguinarine (Sang) on HCC and its potential mechanisms. Our findings showed that Sang impairs the acidic environment of lysosomes by inhibiting cathepsin D maturation. In addition, Sang inhibited the formation of autolysosomes in RFP-GFP-LC3 transfected cells, subsequently suppressing late mitophagy. Sang also induced reactive oxygen species (ROS)-dependent autophagy and apoptosis in HCC cells, which was significantly attenuated following treatment with a ROS scavenger. Further investigation using autophagy inhibitors revealed that sanguinarine-induced mitochondrial dysfunction and mitophagy led to mitochondrial apoptosis in HCC cells. Immunohistochemical staining of sanguinarine-treated xenograft samples revealed that it initiated and blocked autophagy. In summary, our findings suggest that in HCC cells, Sang impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis. [ABSTRACT FROM AUTHOR]

Objective: Japanese encephalitis (JE) is a critical problem of public health worldwide; however, there is limited data about the clinical features and indicators of outcome in adults with severe Japanese encephalitis. Methods: The clinical manifestations and laboratory study on brain neuroimaging of patients with severe JE were statistically analyzed retrospectively. All patients were followed up for 6 months after discharge. The patients were grouped into good outcome and poor outcome according to the results of the follow-up. Results: This retrospective study consists of 9 adults with severe JE, including 5 cases with poor outcome, defined as the modified Rankin Scale (mRS) scores of greater than or equal to 4 points, and remained ventilator dependent. Typical clinical manifestations of JE include fever (100%), altered consciousness (100%), headache (66.7%), flaccid weakness (66.7%), and status epilepticus (44.4%). Serological examination revealed that a higher percentage of neutrophils and a lower percentage of lymphocytes at admission may be associated with a poor outcome. Abnormal neuroimaging of the thalamus (85.7%), hippocampal (71.4%), midbrain (28.6%), and basal ganglia (14.3%) was found. 42.9% of patients left severe irreversible disability, and the most prominent were mental symptoms (71.4%) and memory or understanding disorder (57.1%). Conclusion: Our data suggest that respiratory failure is one of the important causes of early death. Serologic examination, coma, and status epilepticus may indicate a poor outcome for severe JE. Additionally, the hippocampus is the second most common lesion in the adults with severe JE. A large-scale clinical trial is required to further confirm these conclusions. [ABSTRACT FROM AUTHOR]

Previous researches had emphasized tectonic impacts on the fluvial system at the tectonically active areas, while the effects of lithology and local base level change have received relatively rare attention. Here we investigated fluvial landforms at different spatial scales, focusing on knickpoints and channel network reorganization from an area affected by the Haiyuan Fault in the northeastern Tibetan Plateau. The geomorphic indices, i.e., drainage pattern and χ anomalies, were calculated and investigated. The results show that two regional radial drainages formed around the Laohu and Hasi Mountains. Within the interior of the radial drainage, tributaries from the southeast side of the Laohu Mountain experienced near 180° direction change. We interpret this as the gradual drainage capture originating from the height difference (~190 m) of the local base level between the two catchments. Some tributaries from the Hasi Mountain show alternating gorges and broad valleys controlled by lithology. Besides, tectonic uplift and the lowering of base level (from the incision of the Yellow River) triggered an autogenic positive-feedback transition from parallel to dendritic drainage patterns. These observations suggest that base level change and lithology play a crucial role in landscape evolution, even in a tectonically active region. [ABSTRACT FROM AUTHOR]

Background: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown.Methods: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL.Results: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1.Conclusion: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification. [ABSTRACT FROM AUTHOR]

CRISPR-based transcriptional activation is a powerful tool for functional gene interrogation; however, delivery difficulties have limited its applications in vivo. Here, we created a mouse model expressing all components of the CRISPR-Cas9 guide RNA-directed Synergistic Activation Mediator (SAM) from a single transcript that is capable of activating target genes in a tissue-specific manner. We optimized Lipid Nanoparticles and Adeno-Associated Virus guide RNA delivery approaches to achieve expression modulation of one or more genes in vivo. We utilized the SAM mouse model to generate a hypercholesteremia disease state that we could bidirectionally modulate with various guide RNAs. Additionally, we applied SAM to optimize gene expression in a humanized Transthyretin mouse model to recapitulate human expression levels. These results demonstrate that the SAM gene activation platform can facilitate in vivo research and drug discovery. CRISPR-Cas9 is a gene editing tool that can be used to modulate gene expression. Here, the authors report the generation of a mouse model that express all components of the CRISPR-Cas9 guide directed Synergistic Activation Mediator (SAM), demonstrate that gene activation can be achieved with various delivery methods and include generation of a disease model of hypercholesterolemia [ABSTRACT FROM AUTHOR]

The thermal effect on the flow and dispersion of pollutants emitted from a rooftop stack is investigated by means of CFD (computational fluid dynamics) models with wind tunnel experimental validations. The leeward wall and its nearby ground are heated simultaneously to mimic solar radiation. Seventeen Ri (Richardson number) cases with four inflow wind speeds (1, 3, 6, and 9 m/s) and five temperature differences (0, 60, 120, 180, and 240 K) between the heated surface and ambient air are considered to represent the interaction between thermal buoyancy force and inertia force. The results reveal that (1) the steady RANS (Reynolds Averaged Navier-Stokes) computations with Boussinesq approximation can generally reproduce the effect of thermal buoyancy on the wake flow and pollutant distribution in wind tunnel experiments; (2) the wake vortex flow is less affected by the thermal buoyancy force at small Ri (e.g., Ri ≤ 0.26) while an upward flow rather than a clockwise vortex structure is developed in the near wake at Ri ≥ 0.58; (3) it is inappropriate to place fresh air intakes on the leeward wall of the emitting building, but natural ventilation through windows on the leeward wall can be implemented at higher Ri (e.g., Ri = 2.33); (4) at the pedestrian respiration height downstream of the building, the distance between the location of maximum pollutant concentration and the leeward wall increases linearly with Ri while the maximum dimensionless concentration decreases exponentially with increasing Ri; (5) the air temperature is rapidly reduced away from the heated wall/ground and a heat accumulation zone is formed at the ground corner next to the leeward wall. This study can be helpful for determining the strategy for natural ventilation through windows and for evaluating the impacts of rooftop stack exhaust on air quality downstream of emitting buildings. [ABSTRACT FROM AUTHOR]

Avian leukosis caused by avian leukosis virus (ALV) is one of the most severe diseases endangering the poultry industry. When the eradication measures performed in commercial broilers and layers have achieved excellent results, ALV in some local chickens has gradually attracted attention. Since late 2018, following the re-outbreak of ALV-J in white feather broilers in China, AL-like symptoms also suddenly broke out in some local flocks, leading to great economic losses. In this study, a systematic epidemiological survey was carried out in eight local chicken flocks in Jiangxi Province, China, and 71 strains were finally isolated from 560 samples, with the env sequences of them being successfully sequenced. All of those new isolates belong to subgroup J but they have different molecular features and were very different from the strains that emerged in white feature broilers recently, with some strains being highly consistent with those previously isolated from commercial broilers, layers and other flocks or even isolated from USA and Russian, suggesting these local chickens have been acted as reservoirs to accumulate various ALV-J strains for a long time. More seriously, phylogenetic analysis shows that there were also many novel strains emerging and in a separate evolutionary branch, indicating several new mutated ALVs are being bred in local chickens. Besides, ALV-J strains isolated in this study can be further divided into ten groups, while there were more or fewer groups in different chickens, revealing that ALV may cross propagate in those flocks. The above analyses explain the complex background and future evolution trend of ALV-J in Chinese local chickens, providing theoretical support for the establishment of corresponding prevention and control measures. [ABSTRACT FROM AUTHOR]

Nanoflower-like ZnO–C3N4 thin film with a porous net structure was successfully synthesized by a simple chemical corrosion method. The prepared ZnO–C3N4 thin films presented remarkable photocatalytic activities for the degradation of methyl orange under visible light irradiation, and more than 90% methyl orange was removed from water by ZnO–C3N4 composite. Meanwhile, the ZnO–C3N4 composite presented an enhanced photocatalytic stability. The loading content of C3N4 had a great effect on the photocatalytic performance. Moreover, the photocatalytic activities were higher in acidic media than those in alkaline conditions. The adsorption of methyl orange was enhanced, and the recombination of photogenerated electrons and holes was suppressed with a suitable content of C3N4. However, too much loading content of C3N4 resulted in a poor dispersion of C3N4 as the aggregated C3N4 can behave as recombination centers. In addition, the prepared ZnO–C3N4 thin film can be used for the water splitting in water–methanol system under simulated solar light irradiation. [ABSTRACT FROM AUTHOR]

The Yinwashan and Xinminpu faults are located in the Jiuxi Basin in the western end of the Hexi Corridor. The determination of their activity and slip rates is of great significance for understanding the eastward extension of the Altyn Tagh fault. Based on geological and geomorphologic field survey, trench excavation, optically stimulated luminescence dating, we define the fault geometry and kinematic properties of the two faults. Based on fault scarps measurement using differential GPS and 10Be surface exposure dating, we determined vertical slip rate of 0.09±0.01 mm/yr for the Yinwashan fault and 0.1±0.02 mm/yr for the Xinminpu fault. Using the dips observed in trenches and natural sections, we estimated horizontal shortening rates of 0.05±0.03 and 0.23±0.06 mm/yr, respectively. No significant strike slip motion is observed on these two faults, and we infer that this region was dominated by horizontal shortening in the Late Quaternary. Although the shortening rate is quite low on each individual fault, together with other faults in this area, these two faults have an essential role in transferring slip from the eastern end of the Altyn Tagh fault and in accommodating the northeastward growth of Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Artificial insemination is common practice in mass livestock farming. Recently, it was shown that chemicals leaching from multilayer plastic bags affect the fertility of boars, although common quality tests did not show any impact on the sperm. It is not clear whether this incidence was a single case or whether it could be a systematic problem. Therefore, we studied six multilayer plastic bags. A total of 49 compounds were found, but most of them were at very low intensity. Nonylphenols in the range of 19-99 μg/g plastic were found. Migration tests using water and 10% ethanol as simulants, to mimic the behavior of semen with the extender, were performed. The most interesting migrants in terms of potential reprotoxicity were identified as nonylphenols. The identification in depth demonstrated the presence of 10 isomers of nonylphenol with a total concentration range between 16 to 58 μg/Kg simulant, among other migrants at lower concentration. The influence of these nonylphenols and their maximum tolerable concentration in direct contact with semen from boars was studied. Motility, viability, mitochondrial activity and acrosomes reacted were significantly affected at 10 mg/Kg of nonylphenols in contact with the sperm, but in vitro penetration rate was significantly decreased with only 2 mg/Kg. Insight into the mode of action is also provided. [ABSTRACT FROM AUTHOR]