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This study aims to fabricate heterogeneous CNTs/Al composites with a hierarchical structure using powder metallurgy techniques. The hierarchical composites are composed of alternating layers with and without CNTs. Tensile testing of the as-sintered sample, with a 3.5 mm width and containing 0.5 wt% CNTs, revealed an ultimate tensile strength of 249 MPa and 11.8 % elongation to failure. This shows an improvement in overall mechanical properties while maintaining the superior ductility of the alloy and the high strength of uniform composites. Indicating an effective overcoming of the traditional trade-off between strength and ductility. Several strengthening mechanisms have been discussed, including load transfer, grain refinement, and extra dislocations. Coordinated deformation and retarding effect during crack propagation can significantly enhance ductility. Furthermore, the incorporation of reinforcement increased the thermal conductivity by 18.6% due to the excellent thermal characteristics of CNTs. To investigate the intrinsic principles, a parallel and series model was developed to simulate the arrangement of CNTs in the Al matrix. Molecular dynamics (MD) simulations revealed the heat transfer mechanism through the electron-phonon coupling effect. This study proposes a new approach for creating metal materials that have both strength and ductility, while also improving their thermal conductivity.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and β-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5Aand KCND3, thereby influencing the incidence of VA post-MI.

Mg alloys have the defects of low stiffness, low strength, and high coefficient of thermal expansion (CTE). The composites strategy and its architecture design are effective approaches to improve the comprehensive performance of materials, but the processing difficulty, especially in ceramics forming, limits the control and innovation of material architecture. Here, combined with 3D printing and squeeze infiltration technology, two precisely controllable architectures of AZ91/Al2O3interpenetrating phase composites (IPC) with ceramic scaffold were prepared. The interface, properties and impact of different architecture on IPC performance were studied by experiments and finite element simulation. The metallurgical bonding of the interface was realized with the formation of MgAl2O4reaction layer. The IPC with 1 mm circular hole scaffold (1C-IPC) exhibited significantly improved elastic modulus of 164 GPa, high compressive strength of 680 MPa, and good CTE of 12.91 × 10–6K−1, which were 3.64 times, 1.98 times and 55% of the Mg matrix, respectively. Their elastic modulus, compressive strength, and CTE were superior to the vast majority of Mg alloys and Mg based composites. The reinforcement and matrix were bicontinuous and interpenetrating each other, which played a critical role in ensuring the potent strengthening effect of the Al2O3reinforcement by efficient load transfer. Under the same volume fraction of reinforcements, compared to IPC with 1 mm hexagonal hole scaffold (1H-IPC), the elastic modulus and compressive strength of 1C-IPC increased by 15% and 28%, respectively, which was due to the reduced stress concentration and more uniform stress distribution of 1C-IPC. It shows great potential of architecture design in improving the performance of composites. This study provides architectural design strategy and feasible preparation method for the development of high performance materials.

To improve the strength of Al alloys without severely deteriorating the thermal conductivity, the Cu/Al bimetallic composite comprising penetration architecture was artificially designed and fabricated via the additive manufacturing combined with the squeeze casting. The composite exhibited a good balance of the strength (∼340 MPa) and thermal conductivity (200 W/(m·K)), outperforming the traditional Al alloys. High thermal conduction is attributed to the geometrical Cu scaffold, which provides a rapid pathway for the electron conduction. Simultaneously, the good metallurgical bonding is attained by the formation of the Al2Cu eutectic phase along the interfaces, which effectively enhances the strength of the Cu/Al composite.

Bayesian networks are used to evaluate the reliability of a bipolar operational amplifier (op-amp) and subtracter circuit at different orbital conditions. The total ionizing dose (TID) effects of the op-amp and subtracter are investigated by Co60 gamma ray at the Heilongjiang Academy of Sciences, China, and the dose rate is 100 rad(Si)/s. The most sensitive transistors that dominate the degradation of the output voltage range parameter of the op-amp are identified and the interaction between subtracter modules is studied. The extreme-environment radiation effect technology computer aided design (ERETCAD) code is used to calculate the cumulative distributions of TID under different conditions. Finally, the Bayesian networks are established by combining the experimental results and energy spectra to evaluate the failure probability and predict the lifetime of the devices. This method provides a convenient way for on-orbit failure probability evaluation and lifetime prediction of circuits and systems.

Identifying the impact of native/irradiated traps on electrical properties is vital for the implementation of high-performance gallium oxide (Ga2O3) power devices. In this work, the effect of electron irradiation and isochronal thermal annealing on the electrical properties of vertical Ni/Au $\beta $ -Ga2O3 Schottky barrier diode is explored. Majority and minority carrier traps in Ni/Au $\beta $ -Ga2O3 diode after irradiation and annealing are characterized using deep-level transient spectroscopy (DLTS) technique. We observe three trap states at $E_{\mathrm {V}} + 0.402$ eV (H1), $E_{\mathrm {C}} -0.626$ eV (E1), and $E_{\mathrm {C}} -0.755$ eV (E2), in which electron trap E2 is dominant, and the instability of electrical properties of the tested sample is attributed to the electron trap E2. Combining the formation energies and transition levels of $\beta $ -Ga2O3 intrinsic defects calculated by first-principles method, it is speculated that trap H1 is attributed to V $_{\mathrm {GaI}}- 2$ V $_{\mathrm {OII}}(+5/+3$ ) or V $_{\mathrm {GaII}}- 2$ V $_{\mathrm {OII}}(+3/+1$ ), trap E1 is related to V $_{\mathrm {GaI}} - V_{\mathrm {OI}}(-1/-3$ ) or O $_{\mathrm {ic}}(-1/-2$ ), and trap E2 is associated with O $_{\mathrm {id}}(0/-2$ ) or O $_{\mathrm {GaII}}(-1/-3$ ). Additionally, trap E2 is linked to the extrinsic defect FeGa. Based on the experimental and theoretical calculations of Ni/Au $\beta $ -Ga2O3 diode, the exact physical origin of radiation-induced defects and its annealing derivation process are discussed in detail.

The Extreme-environment Radiation Effect Technology Computer-Aided Design-Environment (ERETCAD-Env) software, compatible with a personal computer (PC) equipped with a discrete graphics card, is designed to dynamically simulate the complex phenomena of space environments and the motion state of on-orbit satellites to establish a model-based digital twin for any spacecraft in space. This article highlights the functions and features of ERETCAD-Env, which contain the main models of space environments, including but not limited to the neutral atmosphere, the plasma environment, the radiation environment, the geomagnetic field, and the solar electromagnetic radiation. Three illustrative simulation examples are presented: 1) simulation of multiple environments for multiple satellites on multiple orbits using multiple models: Demonstrates ERETCAD-Env’s capability to simulate diverse environments for multiple satellites concurrently, using a variety of models; 2) parallel computing technology: Discusses the utilization of parallel computing technology within the program, showcasing its efficiency and speed in calculating space environments; and 3) ability to calculate environment of constellation: Highlights ERETCAD-Env’s capability to calculate the environment for a satellite constellation, showcasing its versatility for designing commercial aerospace applications. As an efficient and valuable tool, ERETCAD-Env plays a crucial role in facilitating the reliable design of on-orbit spacecraft by considering the real space environment. This is particularly significant for the commercial aerospace industry where accurate understanding and simulation of space conditions are paramount.

This work aims to clarify the influence of texture on the corrosion behavior of an as-extruded Mg–8Al-0.5In alloy sheet. The weight loss, hydrogen evolution and electrochemical results show that the sample with strong basal texture has the best corrosion resistance. The morphology examinations show the corrosion product film is thinner and more uniform with less cracks for the sample with (0001) plane. The inhomogeneity of corrosion product in samples with (10-10) and (-12-10) planes is the main cause of poor corrosion performance. The findings of this study confirm the corrosion resistance of Mg alloy could be regulated by controlling texture.

A novel coating on the Mg1Mn alloy was produced by anodic polarization combined with hydrothermal treatment (AP + H) in 0.1 M Na2CO3solution. The microstructure and protection of the coating were evaluated. The coating consisted of MgCO3, Mg(OH)2and MgO, and provided satisfactory protection in 3.5 wt% NaCl with a corrosion rate of 0.07 mm y−1in 72 h. However, after that period, the corrosion rate of the specimen increased due to the damage of the coating. The failure of the coating was strongly related to the second phase particles (e.g. Zr particles) or impurities in the matrix. The AP + H coating is supposed to be used as a primer coating for Mg applications in kitchen ware, biomedical areas or industry.

In this article, we analyzed the interaction mechanism between ionization and displacement defects in SiO2 using experimental and simulation techniques. In the experiment, the gate-controlled lateral p-n-p transistors (GLPNPs) were pretreated by He ions irradiation with different energies, which can create additional oxygen vacancy defects (Vo) at various depth ranges in SiO2. The pretreated GLPNPs were irradiated with $\gamma $ -rays to analyze their response to ionization damage. It can be found that the introduction of additional deep Vo in SiO2 weakens the ionization damage of GLPNPs, and this weakening effect is heavily related to the depth of additional deep Vo. In addition, the TCAD simulation tool was used to investigate the mechanism by which the ionization damage is weakened with additional deep Vo depth. The simulation results show that as the additional deep Vo defect approaches the SiO2–Si interface, the additional deep Vo defect enhances the capture of the holes (or release of electrons), resulting in a decrease in hydrogenated Vo ( $\mathbf {Vo}\mathbf {H}_{\mathbf {2}}^{\mathbf {+}}$ ) concentration, which affects the release of protons and ultimately reduces $N_{\mathrm {it}}$ . Based on the above mechanism, it would be helpful to accurately evaluate the electrical characteristics degradation of bipolar transistors in complex space environments.

When evaluating the radiation damage of charged particles to bipolar junction transistors (BJTs), the additional displacement defects caused by charged particles in oxide cannot be ignored. In this article, we demonstrate that the additional displacement defects can enhance or weaken the ionization damage level of BJTs. Additional displacement defects always weaken ionization damage in p-n-p BJTs and may enhance it in n-p-n BJTs. In addition, in the same BJTs, the response of additional displacement defects in oxide at different depths to ionization damage is also different, which strongly depends on the depth of additional displacement defects. Additional displacement defects in oxide show different results in response to ionization damage in different types of BJTs, which brings complexity to the accurate assessment of the radiation hardness of BJTs. Therefore, in this article, three different types of BJTs are analyzed in detail. In their oxides, the response mechanism of additional displacement defects to ionization damage is analyzed in detail, which provides a reference for improving the evaluation accuracy of more types of BJTs.

The electromagnetic directional solidification (DS) phase separation experiments of high silicon 90 wt.% Si–Ti alloy were performed under various pulling-down speeds. The results showed that Si enriched layer, Si + TiSi2-rich layer and Si–Ti–Fe alloy layer appeared successively in axial direction of ingot after electromagnetic DS of 90 wt.% Si–Ti alloy melt at different pulling-down speeds. Separation of primary Si and segregation mechanism of metal impurities (Fe) during the electromagnetic DS process were controlled by pulling-down speed of ingot and electromagnetic stirring. When pulling-down speed was 5 μm/s, minimum thickness of the Si enriched layer was 29.4 mm, and the highest content of primary Si in this layer was 92.46 wt.%; meanwhile, the highest removal rate of Fe as metal impurity was 92.90%. The type of inclusions in the Si enriched layer is determined by Fe content of segregated Si enriched layer. When the pulling-down speed was 5 μm/s, the inclusions in the Si enriched layer were TiSi2. Finally, when the pulling-down speed reached greater than 5 μm/s, the inclusions in the Si enriched layer evolved into TiSi2+ τ5.

The coaddition of Zn and Ca has great potential to improve the ductility of Mg alloys. Herein, the mechanical properties of an extruded Mg–Zn–Ca solid-solution alloy were studied by quasi-in situ electron backscatter diffraction (EBSD)-assisted slip trace analysis. The dominant deformation mechanisms of the Mg–Zn–Ca alloy were studied, and the origins of enhanced ductility were systematically revealed. The results indicate that most grains deformed by basal slip. In addition, multiple non-basal slip traces were detected (particularly prismatic, pyramidal I < a> , and pyramidal I < c+ a> slip traces), and their activation frequency was promoted with increasing tensile strain. The enhanced participation of non-basal slip systems is believed to play a critical role in achieving homogeneous plastic deformation, thus effectively promoting the ductility of the Mg–Zn–Ca alloy. Furthermore, first-principle calculations revealed that the coaddition of Zn and Ca significantly reduces the unstable stacking fault energy for non-basal slip, which contributes to the activation of non-basal slip systems during plastic deformation.

Paleopalynology evidence and megafossil records indicated that tree fern order Cyatheales, played an important role in Mesozoic terrestrial ecosystem. Few fossil records of the family Thyrsopteridaceae have been reported so far. In the present study, we describe a distinctive fertile pinnule segment of a fern plant preserved in a mid-Cretaceous amber from Myanmar. The well-preserved fertile pinnule is identified as a new species of the extant tree fern genus Thyrsopteris(Thyrsopteridaceae): Thyrsopteris cyathindusian. sp. It represents the second fossil species of Thyrsopteridaceae found in the mid-Cretaceous amber from Myanmar. The new species shows distinctive characteristics of the sporophyll that are considered paleoecologically/paleobiogeographically significant for evolution of the Thyrsopteridaceae.

Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis. In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53and Rb1in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidasoverexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.

The effect of temperature on phase transformation, metallization rate, carbon residue and agglomeration of metal Fe after the pre-reduction of carbon-containing pellets in high-chromium vanadium–titanium magnetite (HCVTM) was investigated. The results indicated that titanomagnetite was finally reduced to metal Fe and (Mg, Fe)Ti2O5without low valence titanium oxide with increasing pre-reduction temperature from 950 to 1,250℃; Vanadium magnetite produces Fe, VO and VC0.88without V, and chromite magnetite produces Fe, Cr2O3, CrCxand a small amount of Cr. With an increase in the pre-reduction temperature, the metallization rate in the metallized pellets gradually increases, while the content of the residual carbon gradually decreases. Meanwhile, the iron particles precipitated on the surface of ore particles begin to soften into strips and finally agglomerate to form spherical iron particles, which leads to the diameter of iron particles increasing from 8.23 to 182.35 μm. When the pre-reduction temperature is 1,250℃, the maximum metallization rate in the metallized pellets is 92.49 wt% and the minimum content of residual carbon is 10.37 wt%.

The influence of SrCl2on the corrosion behavior of magnesium (Mg) in 3.5 wt.% NaCl was evaluated by immersion testing, electrochemical measurement and the examination of the corrosion morphology. A small addition of SrCl2decreased the corrosion rate of Mg. In contrast, an excess of SrCl2increased the corrosion rate of Mg, even higher than that in 3.5 wt.% NaCl. There is a competition effect of the SrCl2on the corrosion behavior of Mg in 3.5 wt.% NaCl. The Sr2+can improve the protection of corrosion product film through the formation of SrCO3. While the Cl−can damage the protection of the corrosion product film. The Mg specimen achieved the best corrosion resistance in 3.5 wt.% NaCl + 0.005 mol L−1SrCl2.

• A criterion based on solidification microstructure was proposed to precisely predict the hot tearing behavior of cast alloys. • A simplified criterion was derived, which is suitable for the case where the eutectic liquid fraction is low. • A hot tearing index for equiaxed grains has been proposed, that is, H T I e = | d T d f s 3 | near f s 1 / 3 = 1. A criterion based on solidification microstructure was proposed to precisely predict the hot tearing behavior of cast alloys, which takes into account the effects of both mechanical and nonmechanical factors. This criterion focuses on the events occurring at the grain boundary, which are determined by the thermal contraction, solidification shrinkage, grain growing and liquid feeding. This criterion responds to a series of factors that affect hot tearing, such as alloy composition, mold design, casting process and microstructure. Its credibility has been validated by studying the hot tearing behavior of Mg-Ce alloys. In conformity with the experimental results, this criterion predicted decrease in the number of rods occurring hot tearing with increasing cerium content. A simplified criterion was derived and validated by Mg-Ce (equiaxed grain) and Mg-Al (columnar grain) alloy systems, which is suitable for the case where the eutectic liquid fraction is low and the liquid feeding can be ignored. In addition, a hot tearing index for equiaxed grains was proposed, that is, | d T / d (f s 1 / 3) | near (f s) 1 / 3 = 1 , and its prediction results were consistent with the hot tearing susceptibility calculated from the experimental results. [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, the wear and friction behavior of nanoscale SiCp (1 vol.%) reinforced Mg composite were investigated. Experiments were carried out by rubbing a GCr15 steel ball on the surface of pin specimens with the different sliding velocities of 0.1, 0.3 and 0.5 m/s at distinctive normal loads of 10, 20, and 30 N, respectively (without the aid of lubricant). Detailed analysis demonstrated that SiCp efficiently block the grain growth and improve the mechanical properties of the composite due to grain refining and dislocation strengthening. As a result, the wear resistance of composite was more prominent s compared with the initial alloy under all test condition. With the increase of sliding speed or load, the wear rate of composite increases gradually. The wear rate is reduced by 12% compared to the alloy, particularly in high load condition. Under low speeds, abrasive wear and slight oxidative wear were prevalent. Subsequently, the wear mechanism transitions to the initial delamination wear as the sliding speed increases. Severe plastic deformation occurs on the surface of the friction sample under high load, and the surface damage is serious.

Magnesium–air battery has been considered promising for electrochemical energy storage or as a conversion device due to its high theoretical energy density and low cost. However, the experimental energy density is far lower than the theoretical value due to the intense hydrogen evolution of the Mg anode upon discharging. Herein, we have successfully developed a novel Mg64Zn36(at. %) alloy via single-phase design. The as-prepared Mg64Zn36anode possesses a high discharge specific capacity of 1302 ± 70 mAh g–1and extraordinarily high efficiency of 94.8 ± 4.9%, which breaks the records of efficiency among all of the reported Mg anodes. The superior high efficiency is attributed to the anodic hydrogen evolution being inhibited by Zn alloying, which passivates the Mg matrix. The intermediate ion Mg+produced during discharging is dramatically limited by the integrated passive film and is totally converted into Mg2+electrochemically through the film. Meanwhile, the uniform discharging products due to the homogeneous microstructure of Mg64Zn36co-contribute to the high efficiency. The design of the Mg–Zn alloy may open a new avenue for the development of Mg–air batteries.

Ionic liquids have a wide engineering application foresight due to their easy and safe storage and handling while are limited by the unclear mechanism of hypergolic ignition. In this study, three dicyanamide-based ionic liquids with different cations, 1-allyl-3-methyl imidazolium ([AMIm]), 1-ethyl-3-methylimidazolium ([EMIm]) and 1-butyl-3-methyl-imidazolium ([BMIm]), are prepared to react with white fuming nitric acid through drop tests. The diameter of ionic droplet is 2.2 ​mm, the impact velocities are controlled at 0.16/0.45/0.62/0.82/1.01 ​m ​s-1by adjusting the dropping height, and the whole reacting process is recorded by three cameras to provide macroscopic, microscopic and infrared details. The promotion effect of impact velocity on hypergolic ignition probability is confirmed for all the ionic liquids, and the minimum impact velocity for successful hypergolic ignition of each ionic liquid was determined. The temperature evolution of hypergolic process shows a non-monotonic trend, and a four-stage process was performed to reveal the hypergolic mechanism. The experimental results indicate that short-chain alkyl and unsaturated substituents in cations are favored for hypergolic ignition, and the datasets are conducive for kinetic model construction.

Zn-doped and Zn-Al co-doped La2O3catalysts were prepared by citric acid sol-gel method and characterized by a series of in situ technologies, to investigate the structure-activity relationship of La2O3-based catalysts in the oxidative coupling of methane (OCM). The in situ XRD results reveal a thermal expansion of the La2O3crystal along the c-axis at high temperature. The H2-TPR results show two types of oxygen species on the La2O3-based catalysts, viz., the strong-binding oxygen species and weak-binding oxygen species; in addition, the XPS results indicate that the strong-binding oxygen species is probably attributed to anion radical O−. The doping with Zn can significantly increase the number of oxygen vacancies in the Zn-doped La2O3catalysts, which can promote the activation of oxygen and generate more strong-binding oxygen species; as a result, the Zn-doped La2O3catalyst shows better performance in OCM in comparison with the unmodified La2O3catalyst. Moreover, the co-doping with Al can promote the dispersion of Zn in La2O3and further raise the number of strong-binding oxygen species in the Zn-Al co-doped La2O3catalysts, which is beneficial to enhance the selectivity to C2+hydrocarbons in the OCM reaction.

Combining hyperthermic intraperitoneal chemotherapy with cytoreductive surgery is the main treatment modality for peritoneal metastatic (PM) carcinoma despite the off‐target effects of chemotherapy drugs and the ineluctable side effects of total abdominal heating. Herein, a laser‐integrated magnetic actuation system that actively delivers doxorubicin (DOX)‐grafted magnetic nanorobot collectives to the tumor site in model mice for local hyperthermia and chemotherapy is reported. With intraluminal movements controlled by a torque‐force hybrid magnetic field, these magnetic nanorobots gather at a fixed point coinciding with the position of the localization laser, moving upward against gravity over a long distance and targeting tumor sites under ultrasound imaging guidance. Because aggregation enhances the photothermal effect, controlled local DOX release is achieved under near‐infrared laser irradiation. The targeted on‐demand photothermal therapy of multiple PM carcinomas while minimizing off‐target tissue damage is demonstrated. Additionally, a localization/treatment dual‐functional laser‐integrated magnetic actuation system is developed and validated in vivo, offering a potentially clinically feasible drug delivery strategy for targeting PM and other intraluminal tumors. This work proposes a real‐time photothermal therapy strategy based on a specifically developed dual‐functional laser‐integrated magnetic actuation system that can regulate the locomotion of magnetic nanorobot collectives against gravity to deliver drugs to potentiate local peritoneal metastatic (PM) thermochemotherapy. This unique delivery modality offers a potentially clinically feasible drug delivery strategy for targeting PM and other intraluminal tumors.

ABSTRACTObesity is an important public-health problem worldwide. This study aimed to determine effects of porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on adipocytes injuries and explore associated mechanisms. Adipocytes were isolated from SD rats. pLVX-XBP1 (XBP1 over-expression) and pLVX-XBP1-RNAi (silencing XBP1) were structured and transfected into adipocytes. All adipocytes were divided into pLVX-NC, pLVX-XBP1, pLVX-NC+Pg-LPS and pLVX-XBP1+ Pg-LPS group. Oil-Red O staining was employed to identify isolated adipocytes. Quantitative real-time PCR (qRT-PCR) was used to examine gene transcription of IL-6, TNF-α, leptin, adiponectin. Western blotting was used to detect Bax and caspase-3 expression. Adipocytes were successfully isolated and identified with Oil-Red O staining. Both XBP1 mimic and XBP1 RNAi were effectively transfected into adipocytes with higher expressing efficacy. XBP1 over-expression significantly aggravated Pg-LPS induced inflammatory response compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS significantly enhanced leptin and inhibited adiponectin expression by up-regulating XBP1 expression (p<0.05). XBP1 silence significantly alleviated Pg-LPS induced inflammatory response and reduced leptin, enhanced adiponectin expression in Pg-LPS treated adipocytes compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS induced apoptosis of adipocytes by enhancing XBP1 expression and modulating Bcl-2/Bax pathway associated molecules. In conclusion, Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) induces adipocytes injuries through modulating XBP1 expression and initialling mitochondria-mediated apoptosis.

The purpose of this study is to purify the LpxA protein of Chlamydia trachomatis(Ct) and prepare the polyclonal antibody against LpxA protein, so as to lay a foundation for studying the function of LpxA protein. The LpxA gene was amplified by PCR. The expression plasmid pET28a-LpxA was constructed by using pET28a as the vector. The fusion protein containing 6 histidine tag was induced by IPTG and purified by Ni2+chromatography gel. The purified His-LpxA protein was used as an immunogen to immunize New Zealand rabbits subcutaneously through the back to prepare polyclonal antibody. Immunoblotting was used to detect the reaction between the antibody and His-LpxA. The determination of polyclonal antibody titer was detected by ELISA. The relative molecular weight of His-LpxA was 32.8 kDa, and it could be expressed in Escherichia coli. The purity of the purified protein was about 95%. After immunizing New Zealand rabbits, the antiserum was able to recognize the recombinant His-LpxA protein with a titer greater than 1:10240. In this study, LpxA protein was successfully purified and antiserum was prepared, which provided an experimental basis for studying the function of LpxA protein.

To investigate the progressive fracture processes around a tunnel triggered by static stress and dynamic disturbance, experiments and numerical simulations were performed. The results show that the spatial distributions of acoustic emission (AE) events become very different as lateral pressure coefficients change. The combined effect of static stress and dynamic disturbance causes the damage around the tunnel, and initial stress conditions control the damage morphology. The blast disturbance cannot fundamentally change the damaged area but will deepen the extent of damage and accelerate the failure speed. The more significant the difference between the vertical and horizontal stresses is, the higher the impact on the tunnel by the dynamic disturbance is. The AE activity recovers to a relatively stable state within a short time after the blast and conforms to power-law characteristics.

During the electromagnetic railgun launching process, there will be a complex flow field with high temperature in the muzzle area because of the high-speed friction, transition and secondary arc-ignition. This paper models the muzzle area of railgun when the projectile is far away from the muzzle, and the dynamic simulation of the flow field with secondary arc in the muzzle area is carried out based on the magneto hydrodynamic equations. Meanwhile, a multi-component plasma transport model is used to analyze the muzzle arc plasma flow process of the mixed gas of Al vapor and the air. Furthermore, the pressure boundary conditions are fitted by the dynamic mesh simulation results. The current and voltage of the muzzle are obtained through the emission experiment of the railgun experimental prototype. We load the current data into the simulation model and the voltage of experiments and simulations are compared, which proves the accuracy of the simulation. Then the plasma temperature and the composition of Al vapor in the muzzle flow process are analyzed in-depth.

Microalgae cultivation has gained tremendous attention in recent years due to its great potential in green biofuel production and wastewater treatment application. Membrane technology is a great solution in separating the microalgae biomass while producing high quality of permeate for recycling. The main objective of this study was to investigate the filtration performance of Ag/GO-PVDF (silver/graphene oxide-polyvinylidene fluoride) membrane in an algal-membrane photoreactor (A-MPR) by benchmarking with a commercial PVDF (com-PVDF) membrane. In this study, Chlorella vulgarismicroalgae was cultivated in synthetic wastewater in an A-MPR for ammoniacal-nitrogen and phosphorus recovery and the wastewater was further filtered using Ag/GO-PVDF and com-PVDF membranes to obtain high quality water. Spectrophotometer was used to analyze the chemical oxidation demand (COD), ammoniacal nitrogen (NH3-N) and phosphate (PO43−). The concentration of proteins and carbohydrates was measured using Bradford method and phenol-sulfuric acid method, respectively. The COD of the synthetic wastewater was reduced from (180.5 ± 5.6) × 10−6 ppm to (82 ± 2.6) × 10−6 ppm due to nutrient uptake by microalgae. Then, the Ag/GO-PVDF membrane was used to further purify the microalgae cultivated wastewater, resulting in a low COD permeate of (31 ± 4.6) × 10−6 ppm. The high removal rate of proteins (100%) and carbohydrates (86.6%) as the major foulant in microalgae filtration, with low membrane fouling propensity of Ag/GO-PVDF membrane is advantageous for the sustainable development of the microalgae production. Hence, the integrated A-MPR system is highly recommended as a promising approach for microalgae cultivation and wastewater polishing treatment.

Serving as neuromorphic hardware accelerators, memristors play a crucial role in large-scale neuromorphic computing. Herein, two-terminal memristors utilizing amorphous indium–gallium-zinc oxide (a-IGZO) are fabricated through room-temperature sputtering. The electrical characteristics of these memristors are effectively modulated by varying the oxygen flow during the deposition process. The optimized a-IGZO memristor, fabricated under 3 sccm oxygen flow, presents a 5 × 103ratio between its high- and low-resistance states, which can be maintained over 1 × 104s with minimal degradation. Meanwhile, desirable properties such as electroforming-free and self-compliance, crucial for low-energy consumption, are also obtained in the a-IGZO memristor. Moreover, analog conductance switching is observed, demonstrating an interface-type behavior, as evidenced by its device-size-dependent performance. The coexistence of negative differential resistance with analog switching is attributed to the migration of oxygen vacancies and the trapping/detrapping of charges. Furthermore, the device demonstrates optical storage capabilities by exploiting the optical properties of a-IGZO, which can stably operate for up to 50 sweep cycles. Various synaptic functions have been demonstrated, including paired-pulse facilitation and spike-timing-dependent plasticity. These functionalities contribute to a simulated recognition accuracy of 90% for handwritten digits. Importantly, a one-selector one-memristor (1S1M) architecture is successfully constructed at room temperature by integrating a-IGZO memristor on a TaOx-based selector. This architecture exhibits a 107on/off ratio, demonstrating its potential to suppress sneak currents among adjacent units in a memristor crossbar.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

The breaking of the out-of-plane symmetry makes a two-dimensional (2D) Janus monolayer a new platform to explore the coupling between ferroelectricity and ferromagnetism. Using density functional theory in combination with Monte Carlo simulations, we report a novel phase-switchable 2D multiferroic material VInSe3with large intrinsic out-of-plane spontaneous electric polarization and a high Curie temperature (Tc). The structural transition energy barrier between the two phases is determined to be 0.4 eV, indicating the switchability of the electric polarizations and the potential ferroelectricity. Carrier doping can boost the Curie temperature above room temperature, attributing to the enhanced magnetic exchange interaction. A transition from the ferromagnetic (FM) state to the antiferromagnetic (AFM) state can be induced by carrier doping in octahedra-VInSe3, while FM coupling is well-preserved in tetrahedron-VInSe3, which can be regulated to be either an XY or Ising magnet at an appropriate carrier concentration. These findings not only enrich the family of high-Tclow-dimensional monolayers but also offer a new direction for the design and multifunctional application of multiferroic materials.

A semi-empirical model based on the mixed potential theory and first principles calculation is developed in this study to analyze the galvanic corrosion of the Mg-Ge alloys composed of Mg and Mg2Ge. The thermodynamic driving force of the Mg matrix dissolution is much stronger than that of the Mg2Ge second phase, and Mg2Ge will serve as the local cathode during the galvanic corrosion. The combination of the large anode equilibrium potential difference between Mg and Mg2Ge, and the Schottky barrier across the interface indicates that the Mg2Ge second phase can prevent the Mg grain from serving as the cathode and impede the electron transfer between the Mg grains. First principles calculations on the kinetics of hydrogen evolution reaction upon Mg2Ge reveal that the rate-determining step is the hydrogen adsorption, which is extremely energetically unfavored but an inevitable intermediate state. The estimated exchange current density of the hydrogen evolution upon Mg2Ge is about 3 orders of magnitude smaller than that on pure Mg. The depressed galvanic corrosion of the Mg-Ge alloys is the simultaneous result of the low hydrogen exchange current upon Mg2Ge and preventing the Mg grains from serving as cathodes by the Mg2Ge second phase. The calculated corrosion potentials of the Mg-Ge alloys in our model agree with the experimental values and our model can be used to guide the design of the corrosion-resistant Mg alloys.

To explore the value of transurethral contrast‐enhanced ultrasonography (CEUS) in the diagnosis and evaluation of female urethral diverticula. This study prospectively enrolled 35 women with periurethral cystic lesions, who underwent preoperative transurethral CEUS at our single center between April 2015 and May 2017. The diagnosis of a urethral diverticulum was made by the detection of microbubbles inside the lesion. Data regarding the structure and ostia of the diverticula were collected and then compared with intraoperative findings. The median (interquartile range) age of the 35 patients was 43 (34–48) years. The most common manifestations were dysuria (43%) and palpable masses (40%). On transurethral CEUS, 20 patients were found to have urethral diverticula. The diverticula involved the proximal, mid, and distal urethra with different sizes. The shapes of the diverticula were simple in 4 patients (20%), U shaped in 8 patients (40%), and circumferential in 8 patients (40%). A total of 23 ostia were identified. Seventeen women (85%) had 1 ostium, and 3 women (15%) had 2 ostia. Twenty‐one diverticular ostia (91%) were located from the 3‐ to 9‐o'clock positions. The median (interquartile range) distance from the diverticular ostia to the bladder neck was 20 (9–31) mm. During surgery, all US presentations correlated well with surgical findings, and 21 patients were confirmed to have urethral diverticula. The transurethral CEUS had sensitivity of 95% and specificity of 100%. Transurethral CEUS is an effective method for identifying the structure and ostium of female urethral diverticula. It may have a potential role in preoperative planning and surgical management.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious respiratory virus causing severe morbidity in pigs worldwide. Control strategies for PRRSV often rely on detecting PRRSV, culling or isolating sick pigs, disinfecting pig barns, vaccination, and monitoring for virus spread. Given the high economic impact of PRRSV on pig farms, there is a great need for rapid and reliable PRRSV detection assays. We compared the performance of 2 commercial reverse-transcription real-time PCR (RT-rtPCR) assays, the VetMAX PRRSV NA and EU reagents (ABI assay) and the PRRSV general RT-rtPCR kit (Anheal assay), for the molecular detection of PRRSV in sera collected from pigs in China. Between June and September 2015, sera were collected from 219 healthy and 104 suspected PRRSV-infected pigs on 4 farms in China. Employing blinding, the 2 assays were run by 2 laboratories (Guangzhou Animal Health Inspection Institute [GAHII] and Sun Yat-sen University [SYSU] laboratories) and compared. Although both assays detected PRRSV with 100% specificity at both laboratories, the sensitivity (95% vs. 78% at GAHII; 94% vs. 72% at SYSU Laboratory) and the reproducibility (kappa value 0.933 vs. 0.931) were slightly better for the ABI assay compared to the Anheal assay.

In order to realize the ballistic control of the railgun and the flight stability of the projectile, a new type of railgun is designed, which can control the muzzle velocity and rotation rate. The method of the muzzle velocity and overload control is to adjust the voltage or other parameters of pulse power supply. It would be easy to change velocity accurately in large wide. Another widespread concern problem is launching the spinning stability projectile by railgun. This paper designed a new structure of additional rails to generate an unsymmetrical magnetic field to produce rotational torque in armature. The structure is simple and can control the rotation rate by linear changing the barrel parameters. The calculation formulas of interior ballistic are derived by Biot-Safar law. The important parameter is the deflection angle of the additional rails relative to the symmetry plane of main rail. The larger the angle, the greater the rotation torque generated in the armature. To maintain the flight stability of the projectile, the barrel structural parameters should be proportional to the projectile structural parameters. When changing the muzzle velocity, the rotation rate will also be the equal proportion change. So that the gyro stability is the same. The experiment proves that the railgun designed in this paper can launch the projectile to rotate. And the rotational projectile may not cause the transition or much arcs. This method expands the application of the railgun.

Generalized stacking-fault energies (GSFEs) of basal-plane stacking faults I 1 and I 2 in Mg alloys have been studied based on first-principles calculations, where 43 alloying elements were considered. It is found that the most contributing features of alloying elements to GSFEs are bulk modulus, equilibrium volume, binding energy, atomic radius and ionization energy. Both bulk modulus and ionization energy exhibit positive relationships with GSFEs, and the others show opposite relationships. Multiple regressions have been performed to offer a quantitative prediction for basal-plane GSFEs in Mg- X systems. GSFEs, alloying effects of elements and the prediction model established within this work may provide guidelines for new Mg alloys design with better ductility. [ABSTRACT FROM AUTHOR]

Genetic variants associated with autism spectrum disorders (ASDs) are enriched in genes encoding synaptic proteins and chromatin regulators. Although the role of synaptic proteins in ASDs is widely studied, the mechanism by which chromatin regulators contribute to ASD risk remains poorly understood. Upon profiling and analyzing the transcriptional and epigenomic features of genes expressed in the cortex, we uncovered a unique set of long genes that contain broad enhancer-like chromatin domains (BELDs) spanning across their entire gene bodies. Analyses of these BELD genes show that they are highly transcribed with frequent RNA polymerase II (Pol II) initiation and low Pol II pausing, and they exhibit frequent chromatin–chromatin interactions within their gene bodies. These BELD features are conserved from rodents to humans, are enriched in genes involved in synaptic function, and appear post-natally concomitant with synapse development. Importantly, we find that BELD genes are highly implicated in neurodevelopmental disorders, particularly ASDs, and that their expression is preferentially down-regulated in individuals with idiopathic autism. Finally, we find that the transcription of BELD genes is particularly sensitive to alternations in ASD-associated chromatin regulators. These findings suggest that the epigenomic regulation of BELD genes is important for post-natal cortical development and lend support to a model by which mutations in chromatin regulators causally contribute to ASDs by preferentially impairing BELD gene transcription.

In this study, the performance enhancement of polyvinylidene fluoride (PVDF) polymer as one of the most hydrophobic membrane material, blended with zinc oxide (ZnO) and zinc oxide/reduced graphene oxide (ZnO/rGO) was investigated. ZnO/rGO composites which acted as inorganic filler were synthesized via a facile precipitation method using zinc nitrate (Zn(NO3)2) as zinc precursor and sodium hydroxide (NaOH) as reducing agent. The synthesized ZnO/rGO composites with various Zn loadings were analyzed in terms of particles size and surface charge. The composites with highest surface charge and smallest particles size were then selected for PVDF membrane fabrication. The membranes were produced via immersion-precipitation method and they were characterized by water permeation test, contact angle, morphology, bovine serum albumin (BSA) rejection, flux recovery and antibacterial activity. Based on the findings, ZnO/rGO composites gave the most hydrophilic effect to the PVDF membranes, resulted in 61% of permeation flux increment in comparison with neat PVDF membranes. Simultaneously, the ZnO/rGO mixed matrix membranes (MMMs) showed the highest BSA rejection of 32% and flux recovery ratio of 48%, implying the improvement of the membranes’ fouling resistance. Besides, there was no release of Zn element in permeate of ZnO/rGO MMMs which implied the strong bonding between ZnO/rGO composite with PVDF membranes. In addition, the superior antibacterial property of ZnO/rGO MMMs showed great potential in biofouling mitigation. Hence, the utilization of ZnO/rGO MMMs was highly recommended in various applications involving fouling and biofouling issues.

Magnesium bipolar plates (BPPs) offer great advantage in realizing the ultra-lightweight target of proton exchange membrane fuel cells (PEMFCs). However, high corrosion tendency limits its application. To improve the corrosion resistance and surface conductivity of the Mg BPPs, a novel Graphite paper/Cu coating is proposed in this study. 24 h potentiostatic polarization results reveal that the corrosion current density of the coated specimen dropped by 4 orders of magnitude than that of bare Mg. In addition, the interfacial contact resistance (ICR) of Mg BPPs at 1.4 MPa was remarkably reduced after coating, from 597.22 mΩ cm2to 5.49 mΩ cm2after the polarization test, respectively, which reached the target set by the U.S. Department of Energy (DOE). The results illustrate that the Graphite paper/Cu coating exhibits excellent anti-corrosion and electrical property, which may offer a promising strategy for the coating design on Mg BPPs for ultra-lightweight PEMFCs.

Mutations in MECP2 cause Rett syndrome (RTT), an X-linked neurological disorder characterized by regressive loss of neurodevelopmental milestones and acquired psychomotor deficits. However, the cellular heterogeneity of the brain impedes an understanding of how MECP2 mutations contribute to RTT. Here we developed a Cre-inducible method for cell-type-specific biotin tagging of MeCP2 in mice. Combining this approach with an allelic series of knock-in mice carrying frequent RTT-associated mutations (encoding T158M and R106W) enabled the selective profiling of RTT-associated nuclear transcriptomes in excitatory and inhibitory cortical neurons. We found that most gene-expression changes were largely specific to each RTT-associated mutation and cell type. Lowly expressed cell-type-enriched genes were preferentially disrupted by MeCP2 mutations, with upregulated and downregulated genes reflecting distinct functional categories. Subcellular RNA analysis in MeCP2-mutant neurons further revealed reductions in the nascent transcription of long genes and uncovered widespread post-transcriptional compensation at the cellular level. Finally, we overcame X-linked cellular mosaicism in female RTT models and identified distinct gene-expression changes between neighboring wild-type and mutant neurons, providing contextual insights into RTT etiology that support personalized therapeutic interventions.

Various sonographic characters of female urethral diverticulum could be observed during the evaluation, including single or multiple diverticula, different sites, diverse shapes, and septa, calculi or neoplasm inside diverticulum, all of which could be clearly displayed on B-TRUS.

The effects of the size of micron SiC particle (SiCp) on the grain refinement, distribution of particle and tensile properties of as-cast AZ31B (Mg–3Al–1Zn–0.3Mn) magnesium matrix composites have been investigated. As the volume fraction of micron SiCp increases to 15 vol%, excellent grain refinement is achieved. Meanwhile, volume fraction of particle is set as same content, grain size of matrix decreases as the size of micron SiCp decreases. This is due to both the uniform distribution and refining effect of the fine particles. The micron SiCp distributes along the grain boundaries. Because of grain refinement strengthening and ceramic phase strengthening effects, the room temperature tensile property of M5-15 has the optimal value of YS 171MPa–UTS 216MPa-EL 0.87 %.

Ferroptosis In article 2202562by Longchen Wang, Jianrong Wu, Tao Ying, and co‐workers, an aciditybiodegradable Ir‐Hemin nanosheet is presented to achieve notable ferroptosis efficacy through multiple regulatory pathways, including SDT‐triggered ROS generation, GPX4 inhibition and HO‐1 upregulation‐mediated endogenous Fe2+elevation. This work paves a new way for future studies exploring nanomaterials as ferroptosis inducers.

Safe and effective strategies are urgently needed to fight against the life‐threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy and surgery, exhibit suboptimal efficacy for malignant tumors owing to the serious side effects, drug resistance and even relapse. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), are emerging therapeutic strategies for localized tumor inhibition, which can produce a large amount of reactive oxygen species (ROS) or elevate the temperature to initiate cell death by non‐invasive irradiation. In consideration of the poor bioavailability of phototherapy agents (PTAs), lots of drug delivery systems have been developed to enhance the tumor targeted delivery. Nevertheless, the carriers of drug delivery systems inevitably bring biosafety concerns on account of their metabolism, degradation, and accumulation. Of note, carrier‐free nanomedicine attracts great attention for clinical translation with synergistic antitumor effect, which is characterized by high drug loading, simplified synthetic method and good biocompatibility. In this review, the latest advances of phototherapy with various carrier‐free nanomedicines are summarized, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy. In this review, the latest trends of carrier‐free nanomedicines for tumor phototherapy are summarized. Moreover, the advantages and challenges of carrier‐free nanomedicines are also discussed, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy.

Mechanochemically activated magnesium(0) metal as a highly active mediator driving direct C-4–H alkylation of pyridines with alkyl halides has been developed. Excellent regioselectivity and substrate scope, including those containing reducible functionalities, free amines, and alcohols, as well as biologically relevant molecules were achieved to access 4-alkylpyridine products. Preliminary mechanistic studies suggested a radical–radical coupling pathway.

When an inaudible sound covert channel (ISCC) attack is launched inside a computer system, sensitive data are converted to inaudible sound waves and then transmitted. The receiver at the other end picks up the sound signal, from which the original sensitive data can be recovered. As a forceful countermeasure against the ISCC attack, strong noise can be used to jam the channel and literally shut down any possible sound data transmission. In this paper, enhanced ISCC whose transmission frequency can be dynamically changed is proposed. Essentially, if the transmitter detects that the covert channel is being jammed, the transmitter and receiver both will switch to another available frequency and re-establish their communications, following the proposed communications protocol. Experimental results show that the proposed enhanced ISCC can remain connected even in the presence of a strong jamming noise source. Correspondingly, a detection method based on frequency scanning is proposed to help to combat such an anti-jamming sound channel. With the proposed countermeasure, the bit error rate (BER) of the data communications over enhanced ISCC soars to more than 48%, essentially shutting down the data transmission, and thus neutralizing the security threat.

Epigenomic reconfiguration, including changes in DNA methylation and histone modifications, is crucial for the differentiation of embryonic stem cells (ESCs) into somatic cells. However, the extent to which the epigenome is reconfigured and the interplay between components of the epigenome during cellular differentiation remain poorly defined. We systematically analyzed and compared DNA methylation, various histone modification, and transcriptome profiles in ESCs with those of two distinct types of somatic cells from human and mouse. We found that global DNA methylation levels are lower in somatic cells compared to ESCs in both species. We also found that 80% of regions with histone modification occupancy differ between human ESCs and the two human somatic cell types. Approximately 70% of the reconfigurations in DNA methylation and histone modifications are locus- and cell typespecific. Intriguingly, the loss of DNA methylation is accompanied by the gain of different histone modifications in a locus- and cell type-specific manner. Further examination of transcriptional changes associated with epigenetic reconfiguration at promoter regions revealed an epigenetic switching for gene regulation—a transition from stable gene silencing mediated by DNA methylation in ESCs to flexible gene repression facilitated by repressive histone modifications in somatic cells. Our findings demonstrate that the epigenome is reconfigured in a locus- and cell type-specific manner and epigenetic switching is common during cellular differentiation in both human and mouse.

Genomic approaches have predicted hundreds of thousands of tissue-specific cis-regulatory sequences, but the determinants critical to their function and evolutionary history are mostly unknown. Here we systematically decode a set of brain enhancers active in the zona limitans intrathalamica (zli), a signaling center essential for vertebrate forebrain development via the secreted morphogen Sonic hedgehog (Shh). We apply a de novo motif analysis tool to identify six position-independent sequence motifs together with their cognate transcription factors that are essential for zli enhancer activity and Shh expression in the mouse embryo. Using knowledge of this regulatory lexicon, we discover new Shh zli enhancers in mice and a functionally equivalent element in hemichordates, indicating an ancient origin of the Shh zli regulatory network that predates the chordate phylum. These findings support a strategy for delineating functionally conserved enhancers in the absence of overt sequence homologies and over extensive evolutionary distances.