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In the context of economic globalization, Chinese enterprises must vigorously develop local brands to enhance their competitiveness and adapt to the competitive situation in the international market. The purpose of this paper was to explore how state-owned brands can occupy a place in the saturated market. This paper applied the concept of Marketing Mix Theory and chose the qualitative analysis method and SWOT analysis method for the brand Li Ning. Through research, this paper found that the quality of goods directly affects consumers' desire to purchase. The better the quality is, the more consumers are willing to buy. Secondly, high prices will reduce consumers' purchases and if the quality of goods is the same, people are more willing to choose cheaper goods. The place also has a significant impact on consumers' purchase intentions. This paper focused on exploring how to enhance the competitiveness of Chinese products to enter the international market, fill the deficiencies of previous research, and guide the direction of Chinese brands.

With the gradual reduction of conventional energy sources, the problem of environmental pollution is becoming more and more serious. Environmentally friendly, efficient and flexible power generation models are widely favored, and microgrids emerge as the times require. Microgrid is a medium and low voltage network including power distribution, storage devices, loads and other equipment. It can operate in grid-connected mode or as a stand-alone system in an island environment, continuing to supply power to users even when the large grid is disrupted. Compared with traditional power grids, microgrids have small capacity and changeable operation modes, making it difficult to locate distribution areas and short-circuit currents. At the same time, it is difficult to trace the faults during operation. So far, microgrids have had a lot of technical issues in operation that need to be resolved quickly. In recent years, IoT technology has developed rapidly. The Internet of Things is a comprehensive network that integrates location services, monitoring services, information identification and monitoring services through information exchange and communication technologies, such as video recognition technology, positioning technology, and wireless sensor technology. In order to monitor the operation mode of the microgrid in real time, find the source of the fault and locate the operation target, based on the Internet of Things technology, this paper installs wireless sensors in the line segment to monitor the line and other applications. This paper uses wireless sensor networks to record positioning variables, processes and data analysis to achieve the accuracy of microgrid operation target positioning. In addition, in order to improve the positioning accuracy of wireless sensor monitoring network and solve the problem of energy limitation, DV-Hop algorithm EB-IDMF algorithm and R-A algorithm are also introduced. Finally, the feasibility of the system is verified through experiments and tests. With the blessing of the positioning algorithm, the positioning accuracy is improved by 4.9%, which has great practical value for the target positioning of microgrid operation.

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Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA.Significance:Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.

BACKGROUND There has been a surge in academic and business interest in software for medical devices (SaMD). SaMD enables medical professionals to streamline existing medical practices and make innovative medical processes such as digital therapeutics a reality. Furthermore, SaMD created a billion-dollar market. However, SaMD is not clearly understood as a technological change and emerging industry. OBJECTIVE This review explores how SaMD develops as an industry, which kinds of products dominate, and the underlying mechanisms that lead to the innovation process of SaMD. METHODS We collected product information on 581 FDA-approved SaMDs from the OpenFDA website and 268 company profiles of the corresponding manufacturers from CrunchBase, Bloomberg, PichBook.com, and other company websites. In addition to assessing the metadata SaMD, we used correspondence and business process analyses to assess the distribution of intended use and how SaMDs interact with other devices during the medical process. RESULTS The current SaMD industry is highly concentrated in medical image processing and radiological analysis. Incumbents in the medical device industry currently lead the market and focus on incremental innovation, whereas new entrants, particularly startups, produce more disruptive innovation. We found that hardware medical device functions as a complementary asset for SaMD, whereas how SaMD interacts with the complementary asset differs according to its intended use. Based on these findings, we propose a regime map that illustrates the SaMD innovation process. CONCLUSIONS The findings of this study suggest that SaMD, as an industry, is nascent and dominated by incremental innovation. The innovation process of the present SaMD industry is shaped by data accessibility, which is key to building disruptive innovation. CLINICALTRIAL Not applicable to the present study

For autonomous driving, it is important to develop safe and efficient decision algorithms to handle multi-vehicle interactions. Game theory is suitable to manage the interactive driving decision modelling, however, common approaches of multi-player game formulation is computationally complex for dynamic and intense interactions. The main contributions of this work are two-fold: 1) a global sorting-local gaming framework, namely GLOSO-LOGA, is proposed to solve the intersection interaction problem for autonomous driving, which can comprehensively consider the advantages of multi-vehicle collaboration and single-vehicle intelligence approaches; 2) an interaction disturbance function is used to quantify the impact of indirect interactions on ego vehicle. To validate the algorithm performances, corner case simulations and human-in-the-loop simulator experiments are carried out, in which a four-armed intersection scenario with various urgent and challenging interaction conditions is used. Results show that compared to the traditional approach that decomposes a multi-vehicle game into multiple two-vehicle games, the proposed algorithm can improve both safety and traffic efficiency in intensively interactive driving scenarios even in complex and urgent cases. It may be potentially applied in handling autonomous vehicle's dynamic interactions with multiple road users.

For autonomous driving, it is important to develop safe and efficient decision algorithms to handle multi-vehicle interactions. Game theory is suitable to manage the interactive driving decision modelling, however, common approaches of multi-player game formulation is computationally complex for dynamic and intense interactions. To overcome this challenge, a global sorting-local gaming framework, namely GLOSO-LOGA, is proposed to solve the intersection interaction problem for autonomous driving, which can comprehensively consider the advantages of multi-vehicle collaboration and single-vehicle intelligence approaches. Further, an interaction disturbance function is used to quantify the impact of indirect interactions on ego vehicle. Then simulations with single and multiple conflict areas settings in a four-armed intersection are carried out. Simulations and human-in-the-loop simulator experiments show that the proposed algorithm can improve the interaction safety in intensively interactive driving scenarios even in complex and urgent interaction cases. The proposed framework may be potentially applied in handling autonomous vehicle's dynamic interactions with multiple road users.

Background Enterococcus faecalis (Efa) has been shown to be a “driver bacteria” in the occurrence and development of colorectal cancer (CRC). This study aims to explore the effect of specific metabolites of Efa on CRC. Methods The pro-tumor effects of Efa were assessed in colonic epithelial cells. The tumor-stimulating molecule produced by Efa was identified using liquid chromatography mass spectrometry (LC-MS). The proliferative effect of metabolites on CRC cells in vitro was assayed as well. The concentration of vascular endothelial growth factor A (VEGFA) and interleukin-8 (IL-8) was determined using enzyme-linked immunosorbent assay (ELISA). Tubular formation assay of human umbilical vein endothelial cells (HUVEC) and cell migration assay were applied to study angiogenesis. Additionally, western blot analysis was used to investigate key regulatory proteins involved in the angiogenesis pathway. Tumor growth was assessed using mouse models with two CRC cells and human colon cancer organoid. Results Co-incubation with the conditioned medium of Efa increased the proliferation of cultured CRC cells. Biliverdin (BV) was determined as the key metabolite produced by Efa using LC-MS screening. BV promoted colony formation and cell proliferation and inhibited cell cycle arrest of cultured CRC cells. BV significantly increased the expression level of IL-8 and VEGFA by regulating the PI3K/AKT/mTOR signaling pathway, leading to the acceleration of angiogenesis in CRC. The up-regulation of proliferation and angiogenesis by BV were also confirmed in mice. Conclusion In conclusion, BV, as the tumor-stimulating metabolite of Efa, generates proliferative and angiogenic effects on CRC, which is mainly mediated by the activation of PI3K/AKT/mTOR.

Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA. Significance: Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.

The fractional advection-reaction-diffusion equation plays a key role in describing the processes of multiple species transported by a fluid. Different numerical methods have been proposed for the case of fixed-order derivatives, while there are no such methods for the generalization of variable-order cases. In this paper, a numerical treatment is given to solve a variable-order model with time fractional derivative defined in the Atangana-Baleanu-Caputo sense. By using shifted Gegenbauer cardinal function, this approach is based on the application of spectral collocation method and operator matrices. Then the desired problem is transformed into solving a nonlinear system, which can greatly simplifies the solution process. Numerical experiments are presented to illustrate the effectiveness and accuracy of the proposed method.

Pancreatic cancer is a terminal disease with high mortality and very poor prognosis. A sensitive and quantitative analysis of

In the context of global countries’ pursuit of sustainable development and “dual carbon” goals of China, this paper combines the Tapio decoupling model, Kaya’s equation and LMDI decomposition method to analyze the relationship between carbon emissions and economic growth and the driving factors of carbon emissions in the Yellow River Basin (YRB) of China from 2001 to 2019. It is found that the decoupling state of CO2 and economic growth in the Yellow River Basin shows a trend of expansion negative decoupling - expansion connection - weak decoupling - strong decoupling, but different regions shows some heterogeneity. The economic intensity effect and population size effect generally play a positive role in driving carbon emissions, while carbon emission intensity, industrial structure and energy structure effect play a negative role in driving carbon emissions in most years. From the regional perspective, the energy consumption structure in the middle reaches is the most important factor to promote carbon emissions. In terms of time period, the industrial structure effect is the driving factor of carbon emissions in the decoupling state overall as expansionary linkage, while it is the inhibitor of carbon emissions in the decoupling state overall as weak decoupling. This study also puts forward countermeasures such as optimize the energy structure and upgrade the industrial structure to achieve green and high-quality economic development in the YRB.

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Driving strategy in dynamic environment is crucial to the automated vehicle safety. In extremely emergency scenarios with unavoidable collision (UC), especially those with complex impact patterns, the potential crash risk should be well considered. This paper proposes a crash mitigation (CM) algorithm for UCs, which directly embeds a generalized crash severity index (CSI) model to vehicle-to-vehicle collisions of multiple impact patterns. The idea is that during the short time before a collision, the vehicle will actively adapt its position and poses to minimize the potential crash severity level after the collision. To this end, the generalized CSI model is introduced to estimate the potential crash severity of all sample paths, from which a crash-severity-optimal trajectory is obtained. To improve the inferring time efficiency of the planning module, a neural network is constructed and deployed to approximate the nonlinear severity model. The proposed algorithm is first validated through simulations of UC scenarios, including entry ramp merging, intersection crossing and downhill/uphill crossing. Then for the intersection crossing scenario, the algorithm is deployed to a real car and validated through digital-twin experiments. Results show that by combining the braking and steering interventions for better crash severity reduction, the proposed strategy can achieve better mitigation effects than commonly-used collision avoidance (CA) strategies. This reveals that a new mindset of comprehensive safety strategy should not focus only on CA, but also the last resort of CM if collision is unavoidable. Our work may contribute as a promising solution to the safety problem in emergency scenarios.

Targeting the epidermal growth factor receptor (EGFR) is one of the potential ways to treat glioblastoma (GBM). In this study, we investigate the anti-GBM tumor effects of the EGFR inhibitor SMUZ106 in both in vitro and in vivo conditions. The effects of SMUZ106 on the growth and proliferation of GBM cells were explored through MTT and clone formation experiments. Additionally, flow cytometry experiments were conducted to study the effects of SMUZ106 on the cell cycle and apoptosis of GBM cells. The inhibitory activity and selectivity of SMUZ106 to the EGFR protein were proved by Western blotting, molecular docking, and kinase spectrum screening methods. We also conducted a pharmacokinetic analysis of SMUZ106 hydrochloride following i.v. or p.o. administration to mice and assessed the acute toxicity level of SMUZ106 hydrochloride following p.o. administration to mice. Subcutaneous and orthotopic xenograft models of U87MG-EGFRvIII cells were established to assess the antitumor activity of SMUZ106 hydrochloride in vivo. SMUZ106 could inhibit the growth and proliferation of GBM cells, especially for the U87MG-EGFRvIII cells with a mean IC50 value of 4.36 μM. Western blotting analyses showed that compound SMUZ106 inhibits the level of EGFR phosphorylation in GBM cells. It was also shown that SMUZ106 targets EGFR and presents high selectivity. In vivo, the absolute bioavailability of SMUZ106 hydrochloride was 51.97%, and its LD50 exceeded 5000 mg/kg. SMUZ106 hydrochloride significantly inhibited GBM growth in vivo. Furthermore, SMUZ106 inhibited the activity of U87MG-resistant cells induced by temozolomide (TMZ) (IC50: 7.86 μM). These results suggest that SMUZ106 hydrochloride has the potential to be used as a treatment method for GBM as an EGFR inhibitor.

Herein, Mo2FeB2-based cermets, with nominal composition of Mo2FeB2-2.06Fe-2.9Ni-2.5Cr-xWC-0.04C (x = 0, 2.5, 5, 10 wt %), are fabricated by multi-step sintering to investigate influence of tungsten carbide (WC) content on microstructure and mechanical properties. Results reveal that the microstructure of WC-free cermets resembles that of traditional cermets. However, microstructure of WC-containing cermets (x = 2.5 wt %) is composed of fine black core/grey rim Mo2FeB2 grains and coarse white-colored coreless Fe3(W,Mo)3C grains. Furthermore, at x ≥ 5 wt %, most of white coreless Fe3(W,Mo)3C grains are transformed into a white core/black rim structure. From these observations, it can be concluded that growth of nearly round-shaped Mo2FeB2 grains is through diffusion-control, leading to normal grain growth (NGG), whereas the growth of polyhedral Fe3(W,Mo)3C grains is dictated by the interfacial reactions, resulting in 2D nucleation and partially abnormal grain growth (AGG). In addition, grain size distribution of WC-containing cermets exhibits distinct bimodal characteristics, where average grain size is smaller than that of WC-free cermets. More importantly, presence of WC significantly improves the mechanical properties, resulting in superior fracture toughness of 25.1 ± 0.5 MPa m1/2 and hardness of 90.3 ± 0.1 HRA, at x = 5 wt %, without compromising much of transverse rupture strength.

Complete solid-solution Ti(C,N)-based cermet, with no typical core-rim structure, was synthesized through mechanical activation and subsequent in situ carbothermal reduction method. XRD, SEM, TEM, and C/N analysis were used to investigate the microstructure, phase transformation, and the interfacial characteristics of the present cermets. During solid-state sintering, the (Ti,Mo)C/(Ti,Mo)(C,N) phases formed through the transformation of Mo-based solid solution which generated by mechanical activation. Then, the formed (Ti,Mo)C/(Ti,Mo)(C,N) continuously dissolved into the nickel-based binder above 1100 °C. It was found that in the subsequent stage of liquid sintering, the mechanical activation and also the presence of extremely fine TiC/Ti(C,N) particles accelerated the Mo diffusion into the hard phase, resulting in a large quantity of (Ti,Mo)(C,N) solid solutions formed in the nickel-based binder. Finally, complete (Ti,Mo)(C,N) solid-solution phase was obtained via dissolution and re-precipitation. The higher toughness and transverse rupture strength (TRS) of the synthesized new cermet, as compared with traditional cermets, were mainly caused by the increased crack deflection and transgranular fracture of the novel cermets. Moreover, the interface among the Ni-based binder phase and complete solid solution hard phase exhibited a semi-coherency state with high-density dislocations, which also significantly improved the TRS and toughness of the synthesized cermets.

Herein, Ti(C,N)-based cermets prepared via mechanical activation and subsequent in situ carbothermal reduction was studied. The correlation between microstructural and mechanical performance of these cermets was investigated by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Results indicated that with the increase in tungsten carbide (WC) content, hard particles of ceramic gradually evolved from complete solid solution to partial solid solution with a little quantity of core–rim structure. Mean particle size of the cermet first increased, and then, slightly decreased. In addition, grain shape gradually changed from relatively faceted to nearly round. Initially, with the increase in WC content, the increase in transverse rupture strength (TRS) and slight increase in hardness were related to the strengthening of both solid solution and fine grains. However, with further addition of WC, the decrease in hardness was primarily because of lower hardness of (Ti,W,Mo) (C,N) phase with higher W content. Extremely high toughness of cermets with WC content of 0 and 3 wt% was mainly due to the decrease in interface area compared to traditional cermets, which resulted in significant reduction in interfacial strain between the rim and core. Moreover, toughness improvement of cermets containing 6 to 12 wt% of WC was due to comprehensive effect of superb coherent relationship of black core/grey rim particles, semi-coherent relationship with high-density dislocations of solid-solution particles, and solid-solution strengthening of white core-grey rim particles.

Flexible, robust, and user-friendly screening systems with a large dynamic range are highly desired in scientific research, industrial development, and clinical diagnostics. Droplet-based microfluidic systems with gradient concentrations of chemicals have been demonstrated as promising tools to provide confined microenvironments for screening tests with small reaction volumes. However, the generation and manipulation of gradient droplets, such as droplet merging, generally require sophisticated fluidic manipulation systems, potentially limiting their application in decentralized settings. We present a gradient-droplet SlipChip (gd-SlipChip) microfluidic device that enables instrument-free gradient droplet formation and parallel manipulation. The device can establish a gradient profile by free interfacial diffusion in a continuous fluidic channel. With a simple slipping step, gradient droplets can be generated by a surface tension-driven self-partitioning process. Additional reagents can be introduced in parallel to these gradient droplets with further slipping operations to initiate screening tests of the droplets over a large concentration range. To profile the concentration in the gradient droplets, we establish a numerical simulation model and verify it with hydrogen chloride (HCl) diffusion, as tested with a dual-color pH indicator (methyl orange and aniline blue). As a proof of concept, we tested this system with a gradient concentration of nitrofurantoin for the phenotypic antimicrobial susceptibility testing (AST) of

The purpose of this study was to investigate the effect of percutaneous nephrolithotripsy guided by B-ultrasound in the treatment of complex renal calculi. A total of 82 patients with complex renal calculi were selected, who underwent percutaneous nephrolithotripsy guided by B-ultrasound. The average operation time was 101.52 ±8.35 minutes, the average intraoperative bleeding volume was 132.86 ±7.22 ml, the average hospital stay was 10.47 (±1.68) days, the primary calculi clearance rate was 85.37% (70 cases), and the secondary calculi clearance rate was 95.12% (78 cases). Postoperative complications occurred in 18 (21.95%) cases, including fever in 13 (15.85%), residual stone in 4 (4.88%), and delayed bleeding in 1 (1.22%) case. The findings show that percutaneous nephrolithotripsy guided by B-ultrasound is safe and effective in the treatment of complex renal calculi and is suitable for popularisation and application in primary hospitals. Key words: B-ultrasound; complex renal calculi; percutaneous nephrolithotomy

BackgroundDistant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer “metastases” in liver and lung organ-specific tissues.MethodsLiver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells.ResultsThe response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death.ConclusionsThe therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.

Digital nucleic acid analysis (digital NAA) is an important tool for the precise quantification of nucleic acids. Various microfluidic-based approaches for digital NAA have been developed, but most methods require complex auxiliary control instruments, cumbersome device fabrication, or inconvenient preparation processes. A SlipChip is a microfluidic device that can generate and manipulate liquid partitions through simple movements of two microfluidic plates in close contact. However, the traditional SlipChip requires accurate alignment of microfeatures on different plates; therefore, the dimensions of the microwells and density of partitions can be constrained. Here, we developed a droplet array SlipChip (da-SlipChip) that can form droplets of various sizes at high density in a single slipping step. This process does not require precise overlapping microfeatures on different plates; therefore, the design flexibility and partition density can be significantly increased. We quantified SARS-CoV-2 nucleic acids extracted from the COVID-19 pseudovirus by digital loop-mediated isothermal amplification (LAMP) on a da-SlipChip with 21 696 of 0.25 nL droplets, and the results were in good agreement with those of the commercial digital PCR method of Stilla. Furthermore, we demonstrated a random-access system with a single-throughput fluorescence imager and a stackable thermal control instrument with nine independent heating modules. This random-access system with the da-SlipChip can greatly improve the total throughput and flexibility for digital isothermal nucleic acid quantification and significantly reduce the total waiting time.

Introduction: The aim of this study is to investigate the association between loss of muscle mass and prognosis of sepsis. Methods: Six databases, including PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Ovid, were searched by the deadline of August 18, 2020. A meta-analysis was conducted on the collected data by means of a random-effects model. The quality of each included article was assessed according to the Newcastle-Ottawa Scale. Results: Out of 1,819 references, 6 articles and 1 conference abstract were included. Sepsis patients with a loss of muscle mass or sarcopenia had higher mortality (risk ratio [RR]: 1.94, 95% confidence intervals [CI]: 1.59–2.37; I-squared = 18.7%, p < 0.001). The RR of mortality within 30 days (RR: 2.31, 95% CI: 1.78–2.99, p < 0.001) was higher than that of mortality over 30 days. Loss of psoas muscle mass, as evaluated by CT, showed the highest RR of sepsis mortality. In addition, based on data on overall survival retrieved from 4 trials, the pooled hazard ratio (HR) for patients with a loss of muscle mass or sarcopenia was 3.04. Subgroup analysis showed that survival time was the main source of heterogeneity for the overall HR. Furthermore, the scanning areas of muscle mass in survival patients were 0.33 cm2/m2 higher than those measured in deceased patients. Conclusion: A loss of muscle mass, as evaluated by CT scan, was associated with a poor outcome in sepsis.

A novel Gram-stain-negative, aerobic, yellow-pigmented bacterium was isolated from seawater of Aoshan Bay, and designated as strain ASW18T. Strain ASW18T was a long-rod-shaped bacterium without flagellum and lacked gliding ability. Based on 16S rRNA gene phylogeny, strain ASW18T showed the closest relationship to Croceivirga radicis MCCC 1A06690T, with a sequence similarity of 97.0 %. Strain ASW18T was able to grow at 25–40 °C, at pH 5.5–9.5 and with 0.5–9 % (w/v) NaCl. The genomic DNA G+C content of strain ASW18T was 37.3 %. The predominant cellular fatty acids of strain ASW18T were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The major polar lipids were phosphatidylethanolamine, phosphatidyldimethylethanolamine, an aminolipid and three unidentified lipids. The respiratory quinone of strain ASW18T was menaquinone with six isoprene units (MK-6). Based on the present polyphasic analysis, strain ASW18T represents a novel species of the genus Croceivirga , for which the name Croceivirga litoralis sp. nov. is proposed; the type strain is ASW18T (=MCCC 1K04203T=KCTC 72852T). In addition, it is also proposed that Muricauda lutea should be reclassified as Croceivirga lutea comb. nov.; the type strain is CSW06T (=CGMCC 1.15761T=JCM 31455T=KCTC 52375T=MCCC 1K03195T).

Synechococcus is one group of main primary producers and plays a key role in oceanic carbon fixation and transformation. To explore how the temperature rise affects the bioavailability of Synechococcus-derived dissolved organic matter (SOM) and whether this effect would be altered by the involvement of heterotrophic bacteria, we compared the optical and molecular properties of the SOM of axenic Synechococcus sp. PCC7002 culture (Syn) to that with associated heterotrophic bacteria (SynB) under 15, 18, and 21°C growth temperatures at exponential and decay growth phases. Our results showed that the temperature rise increased the bioavailability of the SOM of both Syn and SynB cultures by lowering the proportion of the hydrogen-poor and double-bond structure-rich humus-like components and highly unsaturated substances, as indicated by the increase of spectral slope ratio (SR) and biological index (BIX) and decrease of humification index (HIX). Moreover, the involvement of heterotrophic bacteria modified the Synechococcus-derived SOM, together with its intracellular dissolved organic matter (DOM) excludes, lowering the SOM bioavailability. Our results indicated that the warming in climate change scenario may enhance the bioavailability of the Synechococcus-derived SOM although it may be tempered by the involvement of heterotrophic bacteria, providing an insight for preservation of the organic carbon pool in global oceans.

Motion planning in dynamic environment is crucial to the automated driving safety. In extremely emergency scenarios with unavoidable collisions, especially those with complex impact patterns, the potential crash risk should be well considered in motion planning. This paper proposes a motion planning algorithm for unavoidable collisions, which directly embeds a generalized crash severity index model to vehicle-to-vehicle collisions of multiple impact patterns. Firstly, the clothoid curve is used to sample the vehicle trajectory before collision, and a two-degree-of-freedom model is adopted to predict the vehicle poses corresponding to each sample path. Then, the crash severity index model is to estimate the potential crash severity of all sample paths. To improve the inferring time efficiency, a neural network is constructed and deployed to approximate the nonlinear severity model. Finally, the crash-severity-optimal trajectory is tracked through model predictive control method. Results show that by combining the braking and steering interventions for better crash severity reduction, the proposed strategy can achieve better mitigation effects than commonly-used collision-avoidance strategies. The deployment of real car experiment and sensitivity analysis demonstrate that the planning algorithm can guarantee real-time and reliably safe performances.

Background: Hirschsprung’s disease (HSCR), a congenital disorder characterized by spasticity and narrowing of the distal colon, as well as abnormalities in peristalsis and defecation, is caused by a deficit of the enteric nervous system of the distal gut. Total colonic aganglionosis (TCA) is a rare type of HSCR. This study aimed to find key microRNAs (miRNAs) and their associated genes from plasma-derived exosomes, as potential biomarkers to study TCA pathogenesis.Results: Plasma-derived exosomal miRNA sequencing of samples from 9 children with HSCR and 10 matched children without HSCR revealed that 62 miRNAs were differentially expressed in plasma-derived exosomes, of which 31 were up-regulated and 31 were down-regulated. The target genes of DEM are predicted from three common databases.There were 652 DEM target gene pairs for the 31 DEMs that were up-regulated and 234 pairs for the 31 DEMs that were down-regulated. Furthermore, 4 DEMs: miR-106b-5p, miR-205-5p, miR-375-3p and miR-34a-5p were differentially expressed between other HSCR types and TCA.Conclusions: Four key miRNAs (miR-106b-5p, miR-205-5p, miR-375-3p, and miR-34a-5p) and their interacting four key genes AF4/FMR2 family member 4 (AFF4), myotubularin-related protein 9 gene (MTMR9), POU domain class 2 transcription factor 1 (POU2F1), and WW-and-C2-domain-containing(WWC2) may be involved in the pathogenesis of TCA.

Background and aim Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. Methods The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). Results We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naive, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). Conclusions In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

In this study, the effects of WO3 content on the microstructure of dual-grain structured hardmetals prepared through in-situ carbothermal reduction of WO3 were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Moreover, mechanical properties of hardmetals with different WO3 content were measured by mechanical property testing devices. Results showed that fine WC grains were formed through in-situ reaction between WO3 and carbon black, and the hardmetals mixed with WO3 exhibited obvious bimodal distribution. As the WO3 content increased, the average WC grain size first decreased and then increased, however, the trend of density change was opposite. Overall, microstructures of hardmetals with a WO3 content of 30 wt% were most homogeneous and dense. Moreover, in hardmetal with a WO3 content of 30 wt%, a low-angle grain boundary at the WC/WC interface was observed. In addition, a perfectly coherent state was observed at the interface between binder phase and fine WC grain formed via in-situ reaction of WO3 and carbon. Both hardness and transverse rupture strength (TRS) first increased and subsequently decreased, while fracture toughness (KIC) initially decreased slightly and then decreased considerably. The dual-grain structured hardmetal with 30 wt% WO3 could achieve a combination of high hardness, TRS and KIC.

The influence of Cr and W addition on microstructure and mechanical properties of Mo2FeB2-based cermets, prepared by multi-step sintering, is systematically evaluated by XRD, SEM, EDS, and TEM. After liquid-phase sintering, the final microstructure of Cr-doped Mo2FeB2-based cermets is similar to that of traditional Mo2FeB2-based cermets. The cermet, with 2.5% Cr content, exhibits superior comprehensive mechanical properties, i.e., Rockwell hardness, transverse rupture strength (TRS) and fracture toughness of 87.6 HRA, 2179 MPa and 21.7 MPa m1/2, respectively. In contrast, for W-doped Mo2FeB2-based cermets, a large amount of W-enriched (Mo,Fe,W)3B2 solid solutions precipitated around undissolved Mo2FeB2 particles, resulting in the formation of black core/gray rim structure. Particularly, a transition layer, with several atomic layer thickness, is observed between (Mo,Fe,W)3B2 rim phase and Fe-based binder phase, which corresponds to B-deficient (Mo,Fe,W)3B2−x orthorhombic boride phase. Moreover, the lattice mismatch between (Mo,Fe,W)3B2 and (Mo,Fe,W)3B2−x is found to be 1.9%. When doped with 5 wt% W, Mo2FeB2-based cermet exhibit superior comprehensive mechanical properties with Rockwell hardness of 84.6 HRA, TRS of 2088 MPa and fracture toughness of 24.4 MPa m1/2. The increase of fracture toughness (KIC) can be ascribed to the presence of W-rich transition layer.

To tackle global water pollution and shortage, solar-driven interfacial water evaporation has been demonstrated as a promising strategy for clean water generation. However, most of the previously reported interfacial evaporation systems only work in rich sunlight, which vastly limits their application under dark conditions. Herein, we propose an all-day solar-driven vapor generator based on metal foam via the photothermal effect in combination with Joule heating. A copper oxide (CuO) needle array and carbon black (CB) nanoparticles were assembled around a copper (Cu) skeleton to obtain CuO/Cu–CB foam with decent interfacial evaporation and salt resistance performance. The water evaporation rate reached 1.65 kg m−2 h−1 under one sun irradiation. Moreover, the vapor generation rate of the device reached 4.50 kg m−2 h−1 when a voltage as low as 2 V was applied. Besides, the CuO/Cu–CB foam can effectively remove the pollutants in the water and the methylene blue (MB) removal efficiency reached ∼98% without any oxide agents after 12 hours of illumination. Therefore, this all-day solar-driven vapor generation device supplies an effective pathway to mitigate freshwater scarcity.

Epidermal growth factor receptor (EGFR) inhibitors represent the first-line treatment of non-small-cell lung cancer (NSCLC). However, the emergence of acquired drug resistance and side effects largely encumbered their application in clinic. The emerging technology proteolysis targeting chimera (PROTAC) could be an alternative strategy to overcome these problems. Herein, we reported the discovery of EGFR

Tropomyosin receptor kinase A (Trk A) is a receptor tyrosine kinase activated by nerve growth factor (NGF). TrkA plays an important role in pain sensation, which leads to significant interest in the development of small molecule inhibitors of TrkA. However, TrkA and the other two highly homologous isoforms, TrkB and TrkC, are highly conserved in the ATP binding site, which suggests that achieving TrkA subtype selectivity over TrkB and TrkC in this site may be extremely challenging. Allosteric inhibitors without making any interactions with the conserved ATP binding site may present a more promising approach. Recently, selective TrkA inhibitors