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The use of Artificial Intelligence (AI) in the context of business decisions of the AG's board of directors brings the company not only opportunities but also major challenges. The first question that arises is whether it is legally permissible to delegate business decisions to AI systems. It is then necessary to consider what skills and knowledge the board of directors should possess to fulfill the new AI-related tasks, and which obligations they should obey to ensure that AI systems will properly and successfully perform the tasks assigned to them. Last but not least, the board of directors must ensure the company’s IT-security when using AI.

Background Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. Methods Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. Results Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. Conclusions Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.

Here, we report the leading manufacture of the large-scale integral weldless stainless steel forging ring (φ = 15.6 m) by the multilayer additive hot-compression bonding technology. Moreover, the detailed interface healing mechanism involving interfacial oxide evolution is elucidated, which validates the feasibility and reliability of the technique we proposed.

Botanical gardens are a primary avenue for ex situ biodiversity conservation. China represents a center of origin for many of the world’s cultivated plants, as well as the birthplace of the world’s earliest pharmacopoeia and most ancient gardens. Botanical gardens are thought to have originated in China, the only one of four ancient civilizations that has persisted without interruption for the last 5000 years. This paper aims to demonstrate the spatiotemporal changes of Chinese botanical gardens and explore their driving mechanism. Based on a systematic review of the literature, the development of Chinese botanical gardens can be roughly divided into three major stages: an enlightenment stage for ancient botanical gardens (2800 BC–1859 AD), a colonial-exploration stage for modern botanical gardens (1860–1949), and a gradual-development stage for modern botanical gardens (1950–2022). By the end of 2022, China will contain a total of 456 botanical gardens, the most of any country in the world; these gardens will cover an area of 115,000 hectares and preserve 515,000 species of living plants. In the past 5000 years, the temporal and spatial development of Chinese botanical gardens has been linked to social and economic developments. By assessing the achievements of each stage of botanical-garden development, four major factors driving the rise, dissemination, development, and evolution of Chinese botanical gardens were identified: societal wealth/prosperity, demand-driven developments, support from science and education fields, and the promotion of ecological sustainability. Our findings fill the gap in botanical-garden development theory, and serve as a reference for the construction and management of botanical gardens.

Adult female mosquitoes rely on olfactory cues like carbon dioxide and other small molecules to find vertebrate hosts to acquire blood. The molecular physiology of the mosquito olfactory system is critical for their host preferences. Many laboratory strains of the yellow fever mosquito Aedes aegypti have been established since the late 19th century. These strains have been used for most molecular studies in this species. Some earlier comparative studies have identified significant physiological differences between different laboratory strains. In this study, we used a Y-tube olfactometer to determine the attraction of females of seven different strains of Ae. aegypti to a human host: UGAL, Rockefeller, Liverpool, Costa Rica, Puerto Rico, and two odorant receptor co-receptor (Orco) mutants Orco2 and Orco16. We performed RNA-seq using antennae of Rockefeller, Liverpool, Costa Rica, and Puerto Rico females. Our results showed that female Aedes aegypti from the Puerto Rico strain had significantly reduced attraction rates toward human hosts compared to all other strains. RNA-seq analyses of the antenna transcriptomes of Rockefeller, Liverpool, Costa Rica, and Puerto Rico strains revealed distinct differences in gene expression between the four strains, but conservation in gene expression patterns of known human-sensing genes. However, we identified several olfaction-related genes that significantly vary between strains, including receptors with significantly different expression in mosquitoes from the Puerto Rico strain and the other strains.

With the rapid development of optical remote sensing, it is urgent to find a reliable target detection method. Compared with traditional detection algorithms, a convolutional neural network has attracted considerable attention owing to its efficiency and high transitivity. However, different from general images, remote sensing images contain complex background information and dense small targets with changeable directions that make detection very challenging. To solve these problems and provide a stable and high-performance detection method, a rotated saliency fusion object detection (RSD) model based on “you only look once” (YOLO)v4 is established. First, salient image fusion technology is used to magnify target information. Second, the angle variable and rotated non-maximal suppression is introduced to improve the accuracy of rotated object detection by including the detection of dense objects. Third, the network structure is enhanced to improve the performance of small-target detection. Finally, the k-means algorithm and data enhancement are introduced to increase the robustness of the model. Extensive experiments demonstrate the superiority of the proposed model in detection speed and accuracy. The mean average precision of the proposed RSD model reaches 97.32% for the remote sensing images in a harbor area with an average detection speed of 13.41 s − 1.

The fat body is considered the insect analog of vertebrate liver and fat tissue. In mosquitoes, a blood meal triggers a series of processes in the fat body that culminate in vitellogenesis, the process of yolk formation. Lipids are stored in the fat body in specialized organelles called lipid droplets that change in size depending on the nutritional and metabolic status of the insect. We surveyed lipid droplets in female Aedes aegypti fat body during a reproductive cycle using confocal microscopy and analyzed the dynamic changes in the fat body lipidome during this process using LC/MS. We found that lipid droplets underwent dynamic changes in volume after the mosquito took a blood meal. The lipid composition found in the fat body is quite complex with 117 distinct lipids that fall into 19 classes and sublcasses. Our results demonstrate that the lipid composition of the fat body is complex as most lipid classes underwent significant changes over the course of the vitellogenic cycle. This study lays the foundation for identifying unknown biochemical pathways active in the mosquito fat body, that are high-value targets for the development of novel mosquito control strategies.

Are social media posts with pictures more popular than those without? Why do pictures with certain characteristics induce higher engagement than some other pictures? Using data sets of social media posts about major airlines and sport utility vehicle brands collected from Twitter and Instagram, the authors empirically examine the influence of image content on social media engagement. After accounting for selection bias on the inclusion of image content, the authors find a significant and robust positive mere presence effect of image content on user engagement in both product categories on Twitter. They also find that high-quality and professionally shot pictures consistently lead to higher engagement on both platforms for both product categories. However, the effect of colorfulness varies by product category, while the presence of human face and image–text fit can induce higher user engagement on Twitter but not on Instagram. These findings shed light on how to improve social media engagement using image content.

Upregulation of histone methyltransferase SET domain bifurcated 1 (SETDB1) is associated with poor prognosis in cancer patients. However, the mechanism of oncogenicity of SETDB1 in cancer is hitherto unknown. Here, we show that SETDB1 is upregulated in human colorectal cancer (CRC) where its level correlates with poor clinical outcome. Ectopic SETDB1 promotes CRC cell proliferation, whereas SETDB1 attenuation inhibits this process. Flow cytometry reveals that SETDB1 promotes proliferation by driving the CRC cell cycle from G0/G1 phase to S phase. Mechanistically, SETDB1 binds directly to the STAT1 promoter region resulting in increased STAT1 expression. Functional characterization reveals that STAT1-CCND1/CDK6 axis is a downstream effector of SETDB1-mediated CRC cell proliferation. Furthermore, SETDB1 upregulation is sufficient to accelerate in vivo proliferation in xenograft animal model. Taken together, our results provide insight into the upregulation of SETDB1 within CRC and can lead to novel treatment strategies targeting this cell proliferation-promoting gene.

High-carbon chromium bearing steels with different rare earth (RE) contents were prepared to investigate the effects of RE on inclusions and impact toughness by different techniques. The results showed that RE addition could modify irregular Al2O3 and MnS into regular RE inclusions. With the increase of RE content, the reaction sequence of RE and potential inclusion forming elements should be O, S, As, P and C successively. RE inclusions containing C might precipitate in molten steel and solid state, but the precipitation temperature was significantly higher than that of carbides in high-carbon chromium bearing steel. For experimental bearing steels, the volume fraction of inclusions increased steadily with the increase of RE content, but smaller and more dispersed inclusions could be obtained by 0.018% RE content compared with bearing steel without RE, whereas the continuous increase of RE content led to an increasing trend for inclusion size and a gradual deterioration for inclusion distribution. RE addition could improve the transverse impact toughness and isotropy of bearing steel, and for modified high-carbon chromium bearing steel by RE alloying, the increase of RE content continuously increased both transverse and longitudinal impact toughness until excessive RE addition.

Two-dimensional layered molybdenum disulfide (MoS2) exhibits great potential for applications in optoelectronic devices, especially photodetectors. However, most of the reported MoS2-based photodetectors only show limited absorption in visible range, resulting in narrow spectral response with poor sensitivity. Integrating plasmonic nanoparticles with MoS2 provides a promising approach to enhance light-matter interactions and detector responsibility. We here report a plasmon-enhanced photodetector based on Au/MoS2 heterostructure with Au nanoparticles (NPs) deposited on the surface of few-layer MoS2 by magnetron sputtering. By coupling with Au NPs, the interactions between ultra-thin MoS2 and incident lights are greatly enhanced via localized surface plasmon resonance. With this new architecture, the spectral response of few-layer MoS2 based photodetector is extended to near-infrared region (700–1600 nm). Further, measurements show that significant improvement of photocurrent is observed with the highest value reaching up to 64 mAW−1 at incident wavelength of 980 nm. With the demonstrated superb performance the proposed detector represents a viable path towards implementing ultra-sensitive near-infrared detection.

In crystalline solids, to computationally determine atomic migration energy barrier is a highly time consuming challenge within the framework of Density Functional Theory (DFT). Through first-principle calculations, here we have proposed a simple, high-throughput formula to fast, effectively calculate atomic migration energy barrier for fcc metals through three basic parameters of materials, the equilibrium volume ( V 0 ), the bulk modulus ( B 0 ) and the Poisson's ratio (ν). This formula is useful not only for the ideal strain-free lattices but also for the uniaxially strained lattices. It has been further validated by a series of fcc metals when compared with both available experimental or theoretical data and DFT-derived data obtained by Nudged Elastic Band (NEB) method. Moreover, we have investigated the effect of uniaxial deformation on the diffusion behavior of vacancy in fcc metals. Our calculations revealed that in fcc metals under uniaxial tensile deformation, vacancy prefers to diffuse along the direction that is perpendicular to the uniaxial tensile deformation.

The effects of different double ageing processes on the mechanical properties and microstructural evolution in the 1460 alloy were investigated. The corresponding microstructure and mechanical properties of the heat-treated specimens were studied by means of transmission electron microscopy, differential scanning calorimetry, hardness testing and tensile testing. The results show that the elongation of two-step aged (130 °C/84 h + 160 °C/24 h) samples can be increased to 8 % with a minor decrease in tensile strength (450 MPa). Throughout the two-step ageing process, the precipitation behaviour of the alloy exhibited the following characteristics: the δ′ phase formed at lower temperature dissolved into the matrix instead of coarsening and becoming over-aged at the beginning of the second ageing step; finely distributed θ′(Al2Cu) and δ′(Al3Li) at a steady state were obtained, resulting in a significant improvement in tensile strength; and the peak ductility occurred with the precipitation of T1(Al2CuLi) and consumption of δ′(Al3Li), as small δ′ particles caused a co-planar slip, resulting in lower ductility.

To understand the effects of nitrogen on precipitation and tensile behaviors at elevated temperatures, 25Cr 20Ni austenitic stainless steels with different nitrogen contents (0.065 wt %, 0.13 wt % and 0.17 wt %) were tensioned from room temperature to 1000 °C. Results show that the elongation and area reduction change differently with temperature increasing from 800 °C to 1000 °C, which are caused by different fracture modes. The necking concentrates in a small zone in the tensile samples of 0.17 wt % N steel, while the necking deformation occurs in all gauge length in specimens of other two steels. The local necking in 0.17 wt % N steel is induced by the enhanced recrystallization softening effect during tensile deformation. As the dislocation recovery are retarded by more solute nitrogen atoms and nitrides in 0.17 wt % N steel, the dislocation density difference between deformed grains and recrystallized grains turns larger, which results in a higher recrystallization rate and enhanced softening effect in further deformation. Additionally, the content of M23C6 precipitates unexpectedly increases with the increasing nitrogen after tensile test at 800 °C. This is because the increasing nitrogen promotes the formation of NbCrN in higher nitrogen steels during solution heat treatment, instead of Nb(C, N) in lower nitrogen steels. The precipitation of NbCrN releases carbon into austenitic matrix, leading to the acceleration of M23C6 precipitation during tensile test at 800 °C.

The microstructure evolutions and the mechanical properties of the 25Cr-20Ni austenitic stainless steel weld metals with different Nb contents were investigated during the long term aging treatment at 700 °C. M23C6, Nb(C, N), α-Cr phase and Nb-nitride phase (Z phase) were observed in the microstructures of the aged weld metals. The results showed that the α-Cr phase precipitated in the interdendritic regions of the weld metals after being exposed to 700 °C for 500 h and the element Nb accelerated the precipitation of the α-Cr phase significantly. The density of the α-Cr phase decreased with the increase of the distance away from the primary Nb(C, N). Additionally, the α-Cr phase showed a crystallographic relationship with the austenitic matrix, [ 1 1 ¯ 1 ¯ ] α-Cr // [ 1 1 ¯ 0 ] γ and ( 01 1 ¯ ) α-Cr // ( 1 ¯ 1 ¯ 1 ) γ. It was observed that the Z phase precipitated in the periphery of the Nb(C, N) and may replace the Nb(C, N) after long term exposure to high temperature. The transformation of the Nb(C, N) into Z phase suggested that the Z phase had a higher stability than the Nb(C, N) particles at 700 °C for long term aging. The tensile strength of the Nb-bearing weld metal showed a continuous decrease at the initial stage of the aging treatment and then went up slightly with the prolonged aging time. However, the elongations and the impact energies of the weld metals decreased monotonously with the increase of the aging time.

The dispersion behaviors of wave propagation in waveguides of piezoelectric helical structures are investigated. By using the tensor analysis in the helical curve coordinate, the general strain − displacement relationship of piezoelectric helix is firstly considered. This paper's formulation is based on the spectral finite element which just requires the discretization of the cross-section with high-order spectral elements. The eigenvalue matrix of the dispersion relationship between wavenumbers and frequencies is obtained. Numerical examples on PZT5A and Ba2NaNb5O15 helical waveguides of a wide range of lay angles are presented. The effects of the piezoelectric on the dispersive properties and the variation tendency of dispersion curves on helix angles are shown. The mechanism of mode separation in piezoelectric helical waveguides is further analyzed through studying waves structures of the flexural modes.

The oxidation behaviour of austenite stainless steel in vacuum and the evolution of oxide scales during vacuum hot-compression bonding were investigated combining XPS and TEM. The results indicate that thick duplex oxide scale with outer MnFe2O4 and inner FeCr2O4 layer was formed in a low vacuum and the complex oxide scale transformed into interfacial oxides MnCr2O4 remaining at the bonding interface after hot-compression bonding at 1200 °C. While in a high vacuum, nanoscale-thick oxide scale with outer Fe3O4 and inner Fe- and Cr-rich layer was observed and it decomposed during the subsequent hot-compression bonding procedure, leading to a well-bonded interface.

The deformation behaviors of 310s stainless steel weld metals (WMs) with different Nb contents are investigated under uniaxial tension at temperatures ranging from ambient temperature to 1000 °C. The results show that Nb effectively improves the strength of the WMs in the whole test temperatures range. The addition of Nb causes a change in the fractures of the WMs from intergranular brittle fractures to intragranular ductile fractures at elevated temperature. Hence, elemental Nb enhances the elevated temperature plasticity of the WMs. However, as the eutectic Nb(C, N) promotes the nucleation and propagation of the cracks, Nb decreases the elongation of the WMs at temperature below 700 °C. With the increase in the deformation temperature, the strength of the WMs decreases monotonously. However, the elongation of the WMs shows a nonmonotonic relationship with the temperatures. The deformation twins can occur at room temperature and improve the strength and elongation of the WMs. Meanwhile, the cracks nucleate around the eutectic Nb(C, N) at 1000 °C, leading to the minimum elongation of the Nb-bearing WMs in the whole test temperature range. The differential scanning calorimetry result suggests that the melting of the eutectic Nb(C, N) may be the dominant reason for the nucleation of the cracks and result in the reduction in the elongation of the Nb-bearing WM at 1000 °C.

The as-quenched microstructure of 2.25Cr-1Mo-0.25 V steel heavy forgings is granular bainite, which is composed of bainitic ferrite and blocky islands of martensite and retained austenite (RA). In this study, the characteristics of RA decomposition and its effects on the mechanical properties of the steel are investigated. The results show that RA decomposes into a cluster of coarse M23C6 carbides and ferrite during standard tempering at 700 °C. These coarse carbides decorate the boundary of the cluster, thus deteriorating the impact toughness of the steel. Accordingly, the size and distribution of these carbides are tentatively modified by introducing pre-tempering at different temperatures ranging from 180° to 650°C before the standard tempering at 700 °C. This is because during pre-tempering, RA first decomposes into various transitional microstructures such as martensite, bainite or pearlite, which further transform into M23C6 carbide clusters during the subsequent 700 °C tempering. The experimental results show that 455 °C is the optimal pre-tempering temperature to improve the impact toughness of the steel after the 700 °C tempering. Microstructural observations reveal that during the 455 °C pre-tempering step, the RA completely decomposes into bainite consisting of fine bainitic packets and a high density of M3C carbides, which provide additional nucleation sites for M23C6 carbides inside the carbide clusters during the subsequent 700 °C tempering, and thus avoid the formation of coarse M23C6 distributed along carbide cluster boundaries.

The biological denitrification for wastewater treatment in winter is often seriously compromised due to the effects of low-temperature (Moraxella osloensis LT-01 was isolated by iterative domestication. The strain LT-01 retained about 60% maximal growth activity at 10 °C. Under initial concentrations of 100 mg/L, average ammonium, nitrate and nitrite removal efficiencies for domestic wastewater (C/N 4:1) at 10 °C were 70.35%, 65.39% and 61.74% in 24 h, respectively. Nitrogen balance analysis showed that about 46% of TN was directed toward in the dissimilation form of gas, and 16% of TN was assimilated for cell growth. Key genes hydroxylamine reductase gene (HAO) and nitrite reductase (NirS) involved in nitrification and denitrification processes were identified by gene-specific PCR, indicating that strain LT-01 perform nitrogen removal efficiently via unique simultaneous nitrification and denitrification. These results suggest the bacterium LT-01 has great potential as an effective performer for treating domestic wastewater in winter.

To effectively solve the serious impact of high oil in the kitchen wastewater on the downstream treatment process, an excellent oil-degrading strain Aeromonas allosaccarophila CY-01 was immobilized to prepare Chitosan-Aeromonas pellets (CH-CY01) by using chitosan as a carrier. Oil degradation condition and efficiency of CH-CY01 pellets were assessed. The growth of immobilized CH-CY01 was almost unaffected, and the maximum degradation rate of soybean oil was 89.7%. Especially at 0.5% NaCl concentration, oil degradation efficiency of CH-CY01 was increased by 20% compared with free cells. In the presence of a surfactant (sodium dodecylbenzene sulfonate) at 1 mg/L, the degradation efficiency of oil by CH-CY01 was increased by 40%. Moreover, using the high-oil catering wastewater as the substrate, more than 80% of the solid oil was degraded with 1% (V/V) CH-CY01 pellets treatment for 7 days, significantly higher than that of free cells. In summary, immobilized CH-CY01 significantly improved the efficiency of oil degradation.为有效解决餐厨废水中的高油脂对下游处理工艺的严重影响，本研究以筛选获得的一株高效的油脂降解菌株嗜糖气单胞菌Aeromonas allosaccarophila CY-01为研究对象，以壳聚糖为载体材料，对其进行固定化包埋制备壳聚糖-气单胞菌小球 (CH-CY01)；探究CH-CY01小球的油脂降解效率以及性能影响评估。研究结果表明，经壳聚糖固定后的菌株CY-01其细胞的生长活性几乎不受影响，对大豆油脂的最大降解率为89.7%；相比于未固定的细胞，CH-CY01在0.5% NaCl的盐度条件下对油脂的降解效率显著提高了20%；在浓度为1 mg/L的表面活性剂 (十二烷基苯磺酸钠) 存在条件下，CH-CY01对油脂的降解效率显著提高了40%。以餐饮高油脂污水为处理对象，结果显示经添加1% (V/V) 的CH-CY01小球处理7 d后，超过80%以上的固态油脂被降解，明显高于未固定的CY-01。综上所述，经壳聚糖固定包埋的CH-CY01小球显著提高了菌株的生存能力和油脂降解效率，对于高油脂餐饮污水的高效处理具有较大的应用潜力。.

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.

We conduct a molecular study on the structural chirality in Langmuir monolayers composed of dipalmitoylphosphatidylcholine (DPPC) using in situ nonlinear optical spectroscopies, including second harmonic generation (SHG) and sum frequency generation (SFG). Chiral SHG response is observed from L-DPPC monolayers at moderate surface pressures and almost vanishes at a high surface pressure. SFG spectra of L-DPPC monolayers show chiral features that can be assigned to the terminal CH3 groups and the CH2 groups attached to the chiral center atom. This means that these achiral moieties form chiral superstructures at the interface. Along with increasing surface pressure, the structural chirality of CH3 groups shows a similar trend as that of chiral SHG, but CH2 chirality increases monotonically. Furthermore, in a racemic DPPC monolayer with a moderate surface pressure, both chiral SHG and chiral SFG of CH3 groups are absent, whereas chiral SFG of CH2 groups is clearly present, indicating that L- and D-DPPC are diastereomers at the air/water interface and interfacial CH2 prefers a certain orientation regardless of the molecular handedness. A molecular mechanism is proposed to explain the origin of the structural chirality in DPPC monolayers.

As the representative of third-generation semiconductor, GaN has been developed rapidly in high temperature and high frequency area in recent years because of its outstanding performance [6]. Although it was not used widely, the characteristics of GaN should be concluded for the further research and realistic application. AlGaN/GaN heterojunction field-effect transistor (HFET) is one of the innovations of the GaN application. This article reviews the characteristics of HFETs in three direction: one is the characteristics of 2DEG in AlGaN/GaN HFETs, second is the basic structure and operation principle of HFETs, the last one is the temperature dependence of AlGaN/GaN HFETs. Based on the software simulation and real data from the former experiments, this paper analyzes the basic characteristics of HFETs.

Background Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL. Methods Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and primary hepatocytes. Results Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in hepatocytes of NAFL mice. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides in hepatocytes of NAFL mice, leading to aggressive hepatic I/R injury with upregulation of oxidative stress and increase of reactive oxygen species (ROS). In contrast, administration of exogenous S1P protected hepatocytes of NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of S1P generation by I/R in liver specimens of NAFL patients. In vitro studies on the L02 human hepatocytes consolidated that inhibiting the generation of S1P by knocking down SPHK1 exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL. Conclusions Generation of S1P by SPHK1 is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lithium-sulfur (Li-S) batteries are highly attractive for their theoretical energy density and natural abundance, but the drawbacks of low sulfur utilization and rapid capacity fade in high-sulfur-loading cathodes still retard their practical use. To enhance kinetics in high-sulfur-loading Li-S cells, it is important to first understand and control the deposition of Li

Me­thio­nine hy­droxy analogue, a common poultry feed supplement, has been obtained in crystalline form for the first time. The asymmetric unit contains two conformationally unequal mol­ecules that are involved in a two-dimensional inter­molecular hydrogen-bonding network., The title compound, a major animal feed supplement, abbreviated as HMTBA and alternatively called dl-me­thio­nine hy­droxy analogue, C5H10O3S, (I), was isolated in pure anhydrous monomeric form. The melting point is 302.5 K and the compound crystallizes in the monoclinic space group P21/c, with two conformationally non-equivalent mol­ecules [(I A) and (I B)] in the asymmetric unit. The crystal structure is formed by alternating polar and non-polar layers running along the bc plane and features an extensive hydrogen-bonding network within the polar layers. The Hirshfeld surface analysis revealed a significant contribution of non-polar H⋯H and H⋯S inter­actions to the packing forces for both mol­ecules.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

Overload of palmitic acids is linked to the dysregulation of ceramide metabolism in nonalcoholic steatohepatitis (NASH), and ceramides are important bioactive lipids mediating the lipotoxicity of palmitic acid in NASH. However, much remains unclear about the role of ceramidases that catalyze the hydrolysis of ceramides in NASH. By analyzing the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, we found that alkaline ceramidase 3 (ACER3) is upregulated in livers of patients with NASH. Consistently, we found that Acer3 mRNA levels and its enzymatic activity were also upregulated in mouse livers with NASH induced by a palmitate-enriched Western diet (PEWD). Moreover, we demonstrated that palmitate treatment also elevated Acer3 mRNA levels and its enzymatic activity in mouse primary hepatocytes. In order to investigate the function of Acer3 in NASH, Acer3 null mice and their wild-type littermates were fed a PEWD to induce NASH. Knocking out Acer3 was found to augment PEWD-induced elevation of C18:1-ceramide and alleviate early inflammation and fibrosis but not steatosis in mouse livers with NASH. In addition, Acer3 deficiency attenuated hepatocyte apoptosis in livers with NASH. These protective effects of Acer3 deficiency were found to be associated with suppression of hepatocellular oxidative stress in NASH liver. In vitro studies further revealed that loss of ACER3/Acer3 increased C18:1-ceramide and inhibited apoptosis and oxidative stress in mouse primary hepatocytes and immortalized human hepatocytes induced by palmitic-acid treatment. These results suggest that ACER3 plays an important pathological role in NASH by mediating palmitic-acid-induced oxidative stress.

The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her‐2/phosphoinositide 3‐kinases (PI3K)/PKB protein kinase (AKT)‐regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER‐2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab‐treated patients. MLH1 loss decreases CTX sensitivity through Her‐2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while MLH1 overexpression increases CTX sensitivity. Blocking Her‐2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her‐2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer., Mismatch repair (MMR) genes deficiency can drive genomic instability and therapeutic resistance in colorectal cancer (CRC). Nevertheless, many of the mechanisms of MMR affecting drug resistance in CRC are still enigmatic. It is revealed that mutL homolog 1 deficiency decreases cetuximab sensitivity through Her‐2/phosphoinositide 3‐kinases/PKB protein kinase signaling, which provides a mechanism of overcoming cetuximab resistance potentially by HER‐2/epidermal growth factor receptor dual inhibition.

Based on first-principles calculations, we predict that the superconductor ${\mathrm{MgB}}_{2}$ with an ${\mathrm{AlB}}_{2}$-type centrosymmetric lattice hosts the so-called phononic topological Weyl nodal lines (PTWNLs) in its bulk phonon spectrum. These PTWNLs can be viewed as countless Weyl points (WPs) closely aligned along the straight lines in the $\ensuremath{-}H--K--H$ direction within the three-dimensional Brillouin zone (BZ) and are always paired with opposite Berry phase. Their topologically nontrivial natures are confirmed by the calculated Berry curvature distributions on the planes perpendicular to these lines. These lines are unique, because they are located exactly at the high-symmetry boundary of the BZ protected by the mirror symmetry and, simultaneously, are straightly transverse to the whole BZ, differently from known classifications, including nodal rings, nodal chains or nets, and nodal loops. On the $(10\overline{1}0)$ crystal surface, the PTWNL-induced drumhead-like nontrivial surface states appear within the rectangular area confined by the projected lines of the PTWNLs. Moreover, when the mirror symmetry is broken, the double-degenerate PTWNLs are further lifted to form a pair of WPs with opposite chirality. Our results pave the way for future experimental study of topological phonons on ${\mathrm{MgB}}_{2}$ and highlight similar results in a series of isostructural ${\mathrm{AlB}}_{2}$-type metallic diborides.

Epithelial-mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with poor patient's prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both in vitro and in vivo, whereas knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Furthermore, the inhibitor of DNA binding 1 (also known as DNA-binding protein inhibitor ID1) was identified as a downstream target of BMP4 using PCR arrays and was upregulated via SMAD1/5/8 phosphorylation. ID1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, ID1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT and promoted GC metastasis by upregulating ID1 expression. Antagonizing BMP4 could be a potential therapeutic strategy for GC metastasis.

Background: Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL. Methods: Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and human cultured hepatocytes. Findings: Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in mouse NAFL. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides, leading to aggressive hepatic I/R injury with increased oxidative stress in NAFL mice. In contrast, administration of exogenous S1P protected NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of SPHK1/S1P pathway by I/R in liver specimens of NAFL patients. In vitro studies on cultured human hepatocytes consolidated that inhibiting the SPHK1/S1P pathway exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL. Interpretations: Activation of SPHK1/S1P pathway is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL. Funding Statement: This work was supported by Dean Foundation of Nanfang Hospital, Southern Medical University (2018C029) to JPQ, Guangdong Province Science and Technology Program (2014A020212174) to CJL, Guangdong Province Science and Technology Program (2017A030313684) to JZ, National Natural Science Foundation of China (81803063) to YYL, National Natural Science Foundation of China (81600462) and the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University (2016006) to KW. Declaration of Interests: The authors declare no competing of interest. Ethics Approval Statement: All experiments using human samples were carried out following the protocols approved by the Medical Ethics Committee of Nanfang Hospital Southern Medical University (NFEC-2019-029).

In recent years, there is a strong interest in thermal cloaking at the nanoscale, which has been achieved by using graphene and crystalline silicon films to build the nanoscale thermal cloak according to the classical macroscopic thermal cloak model. Silicon carbide, as a representative of the third-generation semiconductor material, has splendid properties, such as the high thermal conductivity and the high wear resistance. Therefore, in the present study, we build a nanoscale thermal cloak based on silicon carbide. The cloaking performance and the perturbation of the functional area to the external temperature filed are analyzed by the ratio of thermal cloaking and the response temperature, respectively. It is demonstrated that silicon carbide can also be used to build the nanoscale thermal cloak. Besides, we explore the influence of inner and outer radius on cloaking performance. Finally, the potential mechanism of the designed nanoscale thermal cloak is investigated by calculating and analyzing the phonon density of states (PDOS) and mode participation rate (MPR) within the structure. We find that the main reason for the decrease in the thermal conductivity of the functional area is phonon localization. This study extends the preparation method of nanoscale thermal cloaks and can provide a reference for the development of other nanoscale devices.

The mechanical properties of solid state bonding joints have always been greatly deteriorated due to surface oxide scales. Here, we report a method to completely heal solid state bonding joints with recovered mechanical properties by hot compression bonding and post-holding treatment. Using scanning electron microscopy and transmission electron microscopy, we discovered that the recovery of mechanical properties of the bonding joint is attributed to the dissolution and evolution of the interfacial oxides. While holding the joint at 1200 °C, the interfacial oxides (MnCr2O4) gradually decomposed. With the decomposed oxygen ions diffusing toward the matrix, oxide particles precipitated around both sides of the interface, forming the particle precipitation zone (PPZ). As the holding time increased, the width of the PPZ increased and the oxide precipitates in the PPZ transformed from MnCrxAl2−xO4 to MnxAl3−xO4 and finally to γ-Al2O3, depending on the local oxygen activity. After holding for 24 h, the interfacial oxides completely decomposed and only a few nano-scale γ-Al2O3 oxide precipitates remained dispersed far away from the bonding interface, leading to the recovery of the mechanical properties of the bonding joints. This recovery mechanism may be of great importance to the design and manufacture of high-quality heavy bonding joints. Keywords: Hot compression bonding, Interfacial oxides, Mechanical properties, TEM, Interface healing

This study aims to clarify the effects of aluminum and sulfur content on fatigue property together with corresponding crack initiation and propagation behavior of bearing steel in the very high cycle fatigue (VHCF) regime. For these purposes, ultrasonic tensile-compression fatigue tests were carried out on fatigue specimens with different directions extracted from bearing steel bars containing different aluminum and sulfur content. As a result, high aluminum content in bearing steel leads to worse fatigue property by forming a large collection area of Al2O3 particles. MnS inclusions can cause fatigue failure of low sulfur bearing steel at the 45-degree angle and contribute to fatigue anisotropy. However, there are no MnS inclusions to be found at crack initiation region of failed specimens with ultralow sulfur content. For the VHCF fracture of bearing steel, fracture surface can be simply divided into four different areas according to crack propagation path except fatigue source. The stress intensity factor at the periphery of fine granular area (FGA) ΔKFGA can be regarded as the critical driving force for crack propagating through martensite laths. In addition, crack initiation and propagation are the result of mutual coordination and matching of the driving force ΔK, crack propagation speed and microstructure. Dislocations and precipitated carbides play an important role in the formation of FGA by helping form the corresponding nanoscale grain boundary.