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Nature has long inspired technological innovations, fostering the rapidly developing field of bionics. Inspired by the microstructure of bamboo, we have developed a bamboo-like structure for steel. This novel steel achieves a tensile strength exceeding 1200 MPa and a uniform elongation nearing 68%, resulting in a product of strength and uniform elongation up to 83 GPa·%. The high strength of the steel is primarily attributed to its ultra-fine lamellar grains. Additionally, the graded occurrence of multiple deformation mechanisms collectively maintains its exceptional work-hardening capability. This study presents a new approach to enhancing the performance of medium-Mn steels.

Medium manganese steel represents a promising third-generation advanced high-strength steel. However, achieving excellent plasticity in high-yield-strength medium manganese steel remains challenging, particularly with lower alloying element contents. In this study, we employed an innovative stepwise warm rolling process on 5Mn medium manganese steel, developing a heterolamellar microstructure along the rolling direction. The resulting steel exhibited a yield strength exceeding 1.5 GPa while maintaining a uniform elongation of approximately 29%. The high yield strength is attributed to fine lamellar grains with high dislocation density, while the excellent uniform elongation is due to the synergistic effect of multiple plastic deformation mechanisms, which promoted prolonged strain hardening and delayed the onset of necking. These mechanisms include hetero-deformation induced (HDI) hardening generated during the early deformation of the heterolamellar structure, transformation induced plasticity (TRIP) effect-induced work hardening, and delamination cracking that alleviates interface strain concentration and delays material failure. Collectively, these mechanisms enabled the material to achieve an exceptionally high product of yield strength and uniform elongation of 45 GPa·%. This work provides new insights into the design of high-strength, ductile medium manganese steels, advancing the application of high-performance medium manganese steels.

Abstract It is not clear whether different radiation methods have different effects on enamel. The purpose of this study was to compare the effects of single and fractionated radiation on enamel and caries susceptibility and to provide an experimental basis for further study of radiation‑related caries. Thirty-six caries-free human third molars were collected and randomly divided into three groups (n = 12). Group1 (control group) was not exposed to radiation. Group 2 received single radiation with a cumulative dose of 70 Gy. Group 3 underwent fractionated radiation, receiving 2 Gy/day for 5 days followed by a 2-day rest period, for a total of 7 weeks with a cumulative dose of 70 Gy. Changes in microhardness, roughness, surface morphology, bacterial adhesion and ability of acid resistance of each group were tested. Scanning electron microscope revealed that the enamel surface in both radiation groups exhibited unevenness and cracks. Compared with the control group, microhardness and acid resistance of enamel decreased, while roughness and bacterial adhesion increased in both the single radiation and fractionated radiation groups. Compared with the single radiation group, the enamel surface microhardness and acid resistance decreased in the fractionated radiation group, while roughness and bacterial adhesion increased. Both single radiation and fractionated radiation resulting in changes in the physical and biological properties of enamel, with these changes being more pronounced in the fractionated radiation group. Therefore, fractionated radiation is recommended as a more suitable method for constructing a radiation‑related caries model in vitro.

Abstract Background The aim of the study were as below. (1) To investigate the feasibility of intravoxel incoherent motion (IVIM)-based virtual magnetic resonance elastography (vMRE) to provide quantitative estimates of tissue stiffness in pulmonary neoplasms. (2) To verify the diagnostic performance of shifted apparent diffusion coefficient (sADC) and reconstructed virtual stiffness values in distinguishing neoplasm nature. Methods This study enrolled 59 patients (37 males, 22 females) with one pulmonary neoplasm who underwent computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) with pathological diagnosis (26 adenocarcinoma, 10 squamous cell carcinoma, 3 small cell carcinoma, 4 tuberculosis and 16 non-specific benign; mean age, 60.81 ± 9.80 years). IVIM was performed on a 3 T magnetic resonance imaging scanner before biopsy. sADC and virtual shear stiffness maps reflecting lesion stiffness were reconstructed. sADC and virtual stiffness values of neoplasm were extracted, and the diagnostic performance of vMRE in distinguishing benign and malignant and detailed pathological type were explored. Results Compared to benign neoplasms, malignant ones had a significantly lower sADC and a higher virtual stiffness value (P

Achieving exceptional ductility in ultra-high strength steels has long been a formidable challenge, particularly when the yield strength reaches 2.0 GPa. In this study, we have designed an innovative tri-phase lamellar microstructure in medium Mn steel that successfully achieves both an ultrahigh yield strength of approximately 2.0 GPa and an impressive uniform elongation ranging from 22.5 % to 24.5 %. The ultra-high yield strength of this steel is primarily due to the ultrafine lamellar grain with high-density dislocations and HDI strengthening resulting from meticulously designed tri-phase lamellae. The remarkable ductility is attributed to the synergistic action of multiple plasticity mechanisms. The inherently excellent plasticity of the lamellar ferrite, in coordination with the lamellar martensite, generates significant HDI hardening, thereby suppressing the onset of necking in the early stages of deformation. During the mid-stage of deformation, high strain activates the transformation-induced plasticity effect in the highly stable austenite, which remains stable due to substantial HDI hardening and effectively mitigates strain localization. In the later stages of deformation, delamination cracking relieves stress accumulation at the interfaces, delaying material failure. These mechanisms elevate yield strength and uniform elongation product to 47.3 GPa·%, showcasing the tri-phase lamellar structure’s potential for ultrahigh-strength, high-ductility steels.

Abstract In order to fulfill the complex cognitive behaviors in neuromorphic systems with reduced peripheral circuits, the reliable electronic synapses mimicked by single device that achieves diverse long‐term and short‐term plasticity are essential. Phase change random access memory (PCRAM) is of great potential for artificial synapses, which faces, however, difficulty to realize short‐term plasticity due to the long‐lasting resistance drift. This work reports the ruthenium‐doped Ge2Sb2Te5 (RuGST) based PCRAM, demonstrating a series of synaptic behaviors of short‐term potentiation, pair‐pulse facilitation, long‐term depression, and short‐term plasticity in the same single device. The optimized RuGST electronic synapse with the high transformation temperature of hexagonal phase >380°C, the outstanding endurance >108 cycles, the low resistance drift factor of 0.092, as well as the extremely high linearity with correlation coefficients of 0.999 and 0.976 in parts of potentiation and depression. Further investigations also go insight to mechanisms of Ru doping according to thorough microstructure characterization, revealing that Ru dopant is able to enter GST lattices thus changing and stabilizing atomic arrangement of GST. This leads to the short‐term plasticity realized by RuGST PCRAM. Eventually, the proposed RuGST electronic synapses performs a high accuracy of ~94.1% in a task of image recognition of CIFAR‐100 database using ResNet 101. This work promotes the development of PCRAM platforms for large‐scale neuromorphic systems.

Shallow tunnels in urban areas are close to adjacent buildings and municipal pipelines. Ground surface settlement (GSS) due to tunnelling can cause damage to those infrastructures surrounded. Many methods have been proposed for evaluating ground settlement induced by tunnelling, including empirical, analytical, numerical and artificial intelligence methods. This paper reviews the proposed methods in detail based on published 677 articles within past ten years. The principles, assumptions and application scope of those methods are summarized and the advantages and limitations of each method are discussed. Since artificial intelligence (AI) become popular in recent few years, the application of AI in the aspect of tunnelling-induced ground deformation is introduced emphatically. Finally, the challenges of ground displacement prediction by machine learning (ML) are clarified and future research directions are suggested.

Abstract Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.

Abstract Background Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. Methods RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood–brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein–protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. Results RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. Conclusion RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.

At the initial phases of tunnel design, information on rock properties is often limited. In such instances, the engineering classification of the rock is recommended as a primary assessment of its geotechnical condition. This paper reviews different rock mass classification methods in the tunnel industry. First, some important considerations for the classification of rock are discussed, such as rock quality designation (RQD), uniaxial compressive strength (UCS) and groundwater condition. Traditional rock classification methods are then assessed, including the rock structure rating (RSR), rock mass rating (RMR), rock mass index (RMI), geological strength index (GSI) and tunnelling quality index (Q system). As RMR and the Q system are two commonly used methods, the relationships between them are summarized and explored. Subsequently, we introduce the detailed application of artificial intelligence (AI) method on rock classification. The advantages and limitations of traditional methods and artificial intelligence (AI) methods are indicated, and their application scopes are clarified. Finally, we provide suggestions for the selection of rock classification methods and prospect the possible future research trends.

Fe–Mn–xAl–C steel ingots have been fabricated by vacuum melting with Al compositions varied from x = 0 to 3 and 5 wt.%, respectively. After properly hot-forging and hot-rolling as well as solution heat treatments, impact toughness tests were carried out at 77 K using a standard full-size of Charpy impact V-notch configuration. It was found that the addition of Al element is more conducive to enhance the cryogenic toughness. The relationship between the cryogenic toughness and the Al composition has been revealed through detailed microstructural studies by electron back scatter diffraction and transmission-electron microscopy. The stack fault energy (SFE) increases with the increase of Al content at various temperature. The plastic deformation is dominated by deformation bands which are dominated by deformation twins (DTs) and ε-martensite at x = 0 and DTs at x = 3 and 5%, respectively. The DTs near fracture the notch-tip area increased in the order of the 0Al, 3Al, and 5Al steel. The DTs with high density, together with their contented dislocations, significantly contributed to the high cryogenic toughness of the studied high manganese steel with higher Al content. Banded ε-martensite will deterioration cryogenic toughness due to its large size compared to DTs at 0Al steel.

The hot compression tests of Fe–28Mn–11Al–1.5C–5Cr (wt.%) lightweight steel were carried out by Gleeble-3500 at temperature of 900, 1050 and 1150 °C with strain rates of 0.01 and 1 s−1. The effect of various precipitates on the hot deformation mechanism and dynamic recrystallization (DRX) mechanism was studied by electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). When deformed at 900 °C, the dislocations tend to cut through intragranular κ carbides to form unidirectional microbands and deformation twins. The intergranular precipitates (intergranular κ carbides, B2 (FeAl type) precipitates and (Cr,Mn)23C6 precipitates) hinder the migration of the original grain boundaries, so that the discontinuous DRX (DDRX) is suppressed at the initial stage, but with the increase of strain, the dislocations accumulate at the grain boundaries to promote the nucleation of DRX grains. Meanwhile, the nucleation of DRX grains by continuous DRX (CDRX) mechanism within grains is also activated. Therefore, bimodal distribution of DRX grains is formed at low strain rate of 0.01 s−1, while the degree of DRX is low at high strain rate of 1 s−1. When the deformation temperature is 1050 °C, the content of microbands and deformation twins decreases. There are only a few B2 precipitates at the grain boundaries, so the original grain boundaries tend to bulge to promote DDRX nucleation. When deformed at 1150 °C, large-sized κ carbides are easily formed near the dislocations due to the fast diffusion rate of atoms, which inhibits the formation of microbands and deformation twins, and only slip bands are observed. There is no precipitate on the grain boundary, and the DDRX is the dominant mechanism of DRX. Moreover, the special yield-point-like elongation phenomenon has been proved to be caused by intragranular κ carbides.

In traditional slope stability analysis, it is assumed that some “average” or appropriately “conservative” properties operate over the entire region of interest. This kind of deterministic conservative analysis often results in higher costs, and thus, a stochastic analysis considering uncertainty and spatial variability was developed to reduce costs. In the past few decades, machine learning has been greatly developed and extensively used in stochastic slope stability analysis, particularly used as surrogate models to improve computational efficiency. To better summarize the current application of machine learning and future research, this paper reviews 159 studies of supervised learning published in the past 20 years. The achievements of machine learning methods are summarized from two aspects—safety factor prediction and slope stability classification. Four potential research challenges and suggestions are also given.

In this study, the enhanced passivation effect of Cr-modified rebar compared with carbon rebar has been explored with regard to the formation process of the passive film, which could provide a theoretical basis for the development and application of concrete materials in harsh environments. X-ray photoelectron spectroscopy and capacitance-potential method were used to investigate the composition, structural depth distribution, and semiconductive properties of passive films formed by Cr-modified rebar and carbon rebar in simulated concrete pore solutions with different pH. The kinetics of passive film growth and formation were analyzed by tracking tests of potentiostatic current transients and open circuit potential under natural aeration. The results show that the activation energy of Cr-modified rebar is lower at 14.59 kJ/mol, compared to carbon rebar's 25.36 kJ/mol. In the early stage, Cr-modified rebar can achieve a thinner, more stable initial film in a shorter time than carbon rebar. The rate of reduction of the initial thickening rate of the passive film on Cr-modified rebar is five times than that of carbon rebar per unit pH. The film growth rate after early stage of Cr-modified rebar decreases, whereas that of carbon steel increases, with decreasing pH. The passive film containing Cr oxide or hydroxide enhances the barrier effect of the oxide film to ion migration, and the re-dissociation of Fe oxide hinders the passivation process. This grants the thickness of the stable passive film of the two rebars changing oppositely and the Cr-modified rebar compared to carbon rebar enhance passivation with pH falling.

Carbide-free nano-bainite steel holds significant potential for applications in mining as an ultra-high strength wear-resistant steel, but the wear mechanisms are not yet fully understood. This study aims to explore the effect of austempering temperature on microstructure, mechanical properties and wear resistance of carbide-free nano-bainitic steel. The relationship between the content and mechanical stability of retained austenite (RA) and mechanical properties was investigated to elucidate the mechanisms of pin-on-disc wear and impact wear. The results show that in the range of Ms∼300 °C, the phase transformation incubation period and completion time significantly increase with decreasing austempering temperature, which is mainly related to higher phase transformation driving force resulting from a larger subcooling degree and slow growth of carbon content in RA. Optimal strength and hardness of 2099 MPa and 615 HBW, respectively, are achieved after austempering at 210 °C for 83 h. Austempering at 270 °C for 11 h yields the best balance of strength and plasticity, with a strength-plasticity product of 28.8 GPa%. The micro-cutting mechanism of pin-on-disc wear leads to serious weight loss. The RA with poor mechanical stability accelerates the stress-induced martensite transformation, while internal stress support due to volume expansion reduces the penetration depth of abrasive particles. The weight loss in impact wear is primarily caused by shedding due to fatigue failure. With the increase of RA content and mechanical stability, the persistent stress-induced martensite transformation effectively hinders micro-crack propagation, thereby enhancing impact wear resistance.

A flash tempering process has been demonstrated for low-carbon low-alloy lath martensite, which includes heating the sample to 750 °C (Ac1: 752 °C), dwelling at 750 °C for 2 s, and quenching directly to room temperature. The high temperature accelerated the spread of the supersaturated carbon atoms in the lath martensite, activated the dislocation migrations and thus their combining and annihilation, and promoted the mass recrystallisation. The reduced dwelling time inhibited the coarsening of the martensitic laths and suppressed the growth of the recrystallized structures. The combination of higher temperature and the shorter dwelling period, so-called flash tempering, gives rise to the same microstructure and mechanical properties as those obtained by the conventional tempering process (i.e., dwelling at 600 °C for 1 h). The high efficient flash tempering, possessing significantly reduced energy and time consumptions, may have important consequence in industrialization of tempering process.

Heterostructured austenitic stainless steels (ASS) are becoming a significant research area because of their outstanding mechanical properties and considerable potential for various applications. However, the thermal stability of heterogeneous microstructures, particularly the bimodal microstructure, has received limited attention and lacks systematic investigation. Additionally, there is a scarcity of reports regarding the biocompatibility of bimodal microstructures. Herein, the thermal stability and biocompatibility of the bimodal microstructure prepared by cold rolling and annealing in Cr–Mn–N series ASS (without and with Nb microalloying) are studied. The findings demonstrate that the bimodal microstructures of ASS are formed after annealing at 700 °C, 800 °C, and short-time annealing at 900 °C. Moreover, the addition of Nb significantly enhances the thermal stability of the bimodal microstructure and maintains the bimodal feature up to 1000 °C. The thermal stability of bimodal microstructures depends on the competition in coarse and fine grains growth. The good thermal stability of Nb(C, N) at high temperatures leads to consistently higher pinning force within the fine-grained zone. As a result, the growth of fine grains lags behind that of coarse grains, which leads to the persistence of bimodal microstructure at higher temperatures. The bimodal microstructure of ASS demonstrates superior biocompatibility, attributed to its ability to promote higher cell viability, exhibit stronger fibronectin intensity, and facilitate a wider fibronectin expression network in osteoblasts. These characteristics make the bimodal ASS more favorable for osteoblast attachment and proliferation compared to its coarse-grained counterpart. This study significantly enhances our understanding of the thermal stability and cellular functionality of bimodal ASS, highlighting its potential for various biomedical applications.

In recent years, the development of environmentally friendly, lead-free ferroelectric films with prominent electrostrictive effects have been a key area of focus due to their potential applications in micro-actuators, sensors, and transducers for advanced microelectromechanical systems (MEMS). This work investigated the enhanced electrostrictive effect in lead-free sodium bismuth titanate-based relaxor ferroelectric films. The films, composed of (Bi0.5Na0.5)0.8−xBaxSr0.2TiO3 (BNBST, x = 0.02, 0.06, and 0.11), with thickness around 1 μm, were prepared using a sol-gel method on Pt/TiO2/SiO2/Si substrates. By varying the Ba2+ content, the crystal structure, morphology, and electrical properties, including dielectric, ferroelectric, strain, and electromechanical performance, were investigated. The films exhibited a single pseudocubic structure without preferred orientation. A remarkable strain response (S > 0.24%) was obtained in the films (x = 0.02, 0.06) with the coexistence of nonergodic and ergodic relaxor phases. Further, in the x = 0.11 thick films with an ergodic relaxor state, an ultrahigh electrostrictive coefficient Q of 0.32 m4/C2 was achieved. These findings highlight the potential of BNBST films as high-performance, environmentally friendly electrostrictive films for advanced microelectromechanical systems (MEMS) and electronic devices.

Lead-free bismuth sodium titanate (Bi0.5Na0.5)TiO3 (BNT) and related solid solutions are potential piezoelectric materials for such applications as actuators and transducers if their excellent strain responses and piezoelectric properties can be optimized. In this work, a large strain response of 0.61% is achieved in lead-free (0.94-x%)(Bi0.5Na0.5)TiO3-0.06BaTiO3-x%NaNbO3 (x = 0 –6, BNT-6BT-xNN) ceramics with the composition of x = 3.5 in a pseudo-cubic structure. Coexistence of ferroelectric (FE) and relaxor (RE) domain structures is observed in all the unpoled ceramics and the enhanced strain response is believed to be related to the evolution of the ergodic relaxor (ER) and non-ergodic (NR) states thanks to the substitution of antiferroelectric NN. BNT-6BT-3.5NN is a critical composition near the FE/NR/ER phase boundary close to room temperature (RT) and its high strain response arises from a synergistic combination of a reversible electric-field-induced phase transition and an active domain switching in the mixed NR/ER state. This work provides new insights into the dynamic interplay between mesoscopic domains and macroscopic electrical properties in the BNT-based piezoceramics.

In this study, we investigate the impact of prior ferrite on the bainite transformation kinetics and microstructure of medium-carbon steel interrupted by an intercritical annealing (IAA) process. It was found that the incubation time and completion time decreased from 687 s and 6018 s to 20 s and 4680 s, with the volume fraction of ferrite increasing from 9.5% to 28.6%, while the maximum transformation rate increased from 00271 μm/s to 0.0436 μm/s. The ferrite/austenite interface is introduced, and the nucleation sites are increased to accelerate the subsequent bainite transformation due to the formation of prior ferrite. However, there is a competitive relationship between the number and activation energy of bainite nucleation. According to the experimental results and theoretical calculations, the activation energy of the bainite transformation in the medium-carbon bainite steel decreases gradually with an increase in the volume fraction of prior ferrite.

Abstract Disinfection eliminates pathogenic microorganisms and ensures a biosafe environment for human beings. The rapid spread of COVID-19 is challenging traditional disinfection methods in terms of reducing harmful side effects and conducting faster processes. Spraying large-scale chemical disinfectants is harmful to individuals and the environment, while UV lamp and light-emitting diode (LED) disinfection still requires a long exposure time due to the low irradiance and highly divergent beam characteristics. Given that a laser maintains a high irradiance over a long distance, we studied the effectiveness of lasers as a new disinfection method, and the results show the capability for ultrafast inactivation of SARS-CoV-2 virus with a 266 nm laser. This work confirms UV lasers as a good candidate for disinfection.

Lead-free piezoelectric sodium bismuth titanate (([Formula: see text][Formula: see text])TiO3, BNT) thin films were epitaxially grown onto (001)-, (110)-, and (111)-oriented Nb:SrTiO3 (STO) single crystal substrates prepared by sol–gel processing. Highly oriented growth in (001), (110), and (111) BNT thin films was obtained in this work benefiting from the lattice match between the BNT film and the STO substrate. The different growth models in thin films with various orientations result in various surface morphologies dependent on the film orientation. The piezoresponse of the BNT thin films was represented exhibiting a strong orientation dependence that (110)>(001)>(111). This is contributed by the various domain switching contribution related to the crystal symmetry and polarization distribution in the three oriented thin films.

Although tempering is an effective method to improve the mechanical properties of steel, its influence on corrosion behavior has been controversial. Therefore, we conducted this study to assess the effects of different tempering temperatures on the corrosion resistance of low alloy steel in wet atmosphere using an immersion test, salt spray test, electrochemical measurement, and morphology characterization and phase analysis. The results showed that defects and the highly reactive nature of high angle grain boundaries (HAGBs) of bare steels are preferentially corroded. In the initial stage of corrosion, the tempering temperature affects the distribution of low angle grain boundaries (LAGBs). The specimens tempered at low tempering temperatures corroded lightly because of low interface energy. In the later stage of corrosion, the corrosion resistance of the specimens still depends on the matrix due to the limited protection of the rust layer. Thus, the charge transfer resistance improves and the corrosion resistance becomes better with the decrease of tempering temperature.

The integration of epitaxial complex oxides on semiconductor and flexible substrates is required but challenging. Here, the authors report the highly heterogeneous epitaxy of transferrable BaTiO3-δ membrane with enhanced flexoelectricity on Ge (011).

Objective The aim of this research was to explore the role and potential mechanism of long non-coding RNA PAXIP-AS1 in preeclampsia. Methods To investigate the effects of PAXIP-AS1 on cell viability, migration, and invasion. The miR-210-3p-targeted relationship with lncRNA PAXIP-AS1 or BDNF was verified. Results PAXIP-AS1 was inversely correlated with miR-210-3p and BDNF was targeted by miR-210-3p. BDNF was positively correlated with PAXIP-AS1 in the serum of preeclampsia patients. The promotion effects of PAXIP-AS1 on cell viability, migration, and invasion were reversed by miR-210-3p up-regulation or BDNF knockdown in trophoblast cells. Conclusion PAXIP-AS1 promoted the viability, migration, and invasion of trophoblast cells by regulating the miR-210-3p/BDNF axis.

Hardware electronic synapse and neuro-inspired computing system based on phase change random access memory (PCRAM) have attracted an extensive investigation. However, due to the intrinsic asymmetric reversible phase transition, the defective weight update of PCRAM synapses in aspects of tuning range, linearity and continuity has long required a system-level complexity of circuits and algorithms. The cell-level improvements to a great extent may slim the system thus achieving efficient computing. We report in this work the great enhancement of Ge2Sb2Te5 (GST) based PCRAM synapses by combining materials engineering and pulse programming. It is found that carbon doping in GST retards the rate of phase changing thus increasing the controllability of the conductance, while non-linear programmable pulse excitations can eventually lead to a reliable synaptic potentiation and depression. A set of improved programmable pulse schemes for spike-timing dependent plasticity was then demonstrated, suggesting its potential superiority in flexible programming and reliable data collection. Our methods and results are of great significance for implementing PCRAM electronic synapses and high-performance neuro-inspired computing.

In landslide risk management, it is important to estimate the run-out distance of landslides (or debris flows) such that the consequences can be estimated. This research presents an innovative array of dimensionless equations that effectively estimate run-out distances, supported by both experimental data and numerical simulations. We employ the coupled Eulerian–Lagrangian (CEL) method to confront the challenges presented in large deformations during landslides. The soil is modelled using the Mohr–Coulomb model, and the failure of cohesionless soil slopes (e.g., sand slopes) is studied. The simulation results are used to study the characteristics of flows and run-out distances. We suggest a normalized run-out and introduce new scaling relationships for it under different conditions such as different plane angles and material properties. The granular flows under different scales can be compared directly with this new scaling law. The new relationships are validated by both experimental and numerical data. Our analysis reveals that the normalized run-out distance in debris flows is contingent on the initial geometry, plane angle, and material properties. An increase in debris volume and plane angle can contribute to an increase in the normalized run-out distance, while a rise in friction angles causes a decrease. In the case of landslides, the normalized run-out distance depends on material properties and the slope angle. An increase in slope angle leads to a corresponding increase in the normalized run-out distance.

IntroductionCheckpoint inhibitor pneumonitis (CIP) is a common serious adverse event caused by immune checkpoint inhibitors (ICIs), and severe CIP can be life-threatening. We aimed to investigate the role of peripheral blood cells in diagnosis, prediction, and prognosis evaluation for all and severe CIP.Materials and methodsPatients with lung cancer receiving ICIs were enrolled in this retrospective study. Baseline was defined as the time of ICI initiation, endpoint was defined as the time of clinical diagnosis of CIP or the last ICI treatment, and follow-up point was defined as 1 week after CIP. Eosinophil percentages at baseline, endpoint, and follow-up point were shortened to “Ebas”, “Eend and “Efol”, respectively.ResultsAmong 430 patients included, the incidence of CIP was 15.6%, and severe CIP was 3.7%. The Eend/Ebas value was lower in patients with CIP (p = 0.001), especially severe CIP (p = 0.036). Receiver operating characteristic curves revealed that Eend/Ebas could serve as a biomarker to diagnose CIP (p = 0.004) and severe CIP (p < 0.001). For severe CIP, the eosinophil percentage declined before the symptoms appeared and CT diagnosis. The eosinophil percentage significantly elevated at the follow-up point in the recovery group but not in the non-recovery group. The CIP patients with Efol/Ebas ≥1.0 had significantly prolonged overall survival (p = 0.024) and after-CIP survival (AS) (p = 0.043). The same results were found in severe CIP but without a statistical difference.ConclusionsEosinophil percentage was associated with the diagnosis, prediction, and prognosis of CIP and severe CIP.

Non-invasive approaches to stratify early responses to therapy are of great value to improve cancer patient management. Here the authors design a hybrid nanovesicle-based activatable inflammation magnetic resonance method for the early prediction of response to radiotherapy.

To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019 (COVID-19) based on computed tomography (CT) images. We retrospectively examined 44 confirmed COVID-19 cases. All cases were evaluated separately by radiologists (visually) and through an in-house computer software. The degree of lesions was visually scored by the radiologist, as follows, for each of the 5 lung lobes: 0, no lesion present; 1, 1/3 and 2/3 involvement. Lesion density was assessed based on the proportion of ground-glass opacity (GGO), consolidation and fibrosis of the lesions. The parameters obtained using the computer tool included lung volume (mL), lesion volume (mL), lesion percentage (%), and mean lesion density (HU) of the whole lung, right lung, left lung, and each lobe. The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation. A Chi-square test was used to test the consistency of radiologist- and computer-derived lesion percentage in the right/left lung, upper/lower lobe, and each of the 5 lobes. The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software (r ranged from 0.7679 to 0.8373, P

Abstract Background It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium, plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. Methods The levels of IL-1 β, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells’ apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. Results In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 β, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress. Conclusions The above results collectively suggested that ALT suppressed CSE-induced inflammation, apoptosis and oxidative stress by modulating the NF-ĸB and Nrf2/ HO-1 axis.

With the rapid increase in wind power, its strong randomness has brought great challenges to power system operation. Accurate and timely ultra-short-term wind power prediction is essential for the stable operation of power systems. In this paper, an LsAdam–LSTM model is proposed for ultra-short-term wind power prediction, which is obtained by accelerating the long short-term memory (LSTM) network using an improved Adam optimizer with loss shrinkage (LsAdam). For a specific network topology, training progress heavily depends on the learning rate. To make the training loss of LSTM shrink faster with standard Adam, we use the past training loss-changing information to finely tune the next learning rate. Therefore, we design a gain coefficient according to the loss change to adjust the global learning rate in every epoch. In this way, the loss change in the training process can be incorporated into the learning progress and a closed-loop adaptive learning rate tuning mechanism can be constructed. Drastic changes in network parameters will deteriorate learning progress and even make the model non-converging, so the gain coefficient is designed based on the arctangent function with self-limiting properties. Because the learning rate is iteratively tuned with past loss-changing information, the trained model will have better performance. The test results on a wind turbine show that the LsAdam–LSTM model can obtain higher prediction accuracy with much fewer training epochs compared with Adam–LSTM, and the prediction accuracy has significant improvements compared with BP and SVR models.

BackgroundIt is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope.ObjectiveThis study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage.MethodThe cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly.ResultsWith respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists.ConclusionA deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer’s primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.

Fast and accurate cerebrospinal fluid cytology is the key to the diagnosis of many central nervous system diseases. However, in actual clinical work, cytological counting and classification of cerebrospinal fluid are often time-consuming and prone to human error. In this report, we have developed a deep neural network (DNN) for cell counting and classification of cerebrospinal fluid cytology. The May-Grünwald-Giemsa (MGG) stained image is annotated and input into the DNN network. The main cell types include lymphocytes, monocytes, neutrophils, and red blood cells. In clinical practice, the use of DNN is compared with the results of expert examinations in the professional cerebrospinal fluid room of a First-line 3A Hospital. The results show that the report produced by the DNN network is more accurate, with an accuracy of 95% and a reduction in turnaround time by 86%. This study shows the feasibility of applying DNN to clinical cerebrospinal fluid cytology.

A full understanding of the impact of charge trapping on the memory window (MW) of HfO2-based ferroelectric field effect transistors (FeFETs) will permit the design of program and erase protocols, which will guide the application of these devices and maximize their useful life. The effects of charge trapping have been studied by changing the parameters of the applied program and erase pulses in a test sequence. With increasing the pulse amplitude and pulse width, the MW increases first and then decreases, a result attributed to the competition between charge trapping (CT) and ferroelectric switching (FS). This interaction between CT and FS is analyzed in detail using a single-pulse technique. In addition, the experimental data show that the conductance modulation characteristics are affected by the CT in the analog synaptic behavior of the FeFET. Finally, a theoretical investigation is performed in Sentaurus TCAD, providing a plausible explanation of the CT effect on the memory characteristics of the FeFET. This work is helpful to the study of the endurance fatigue process caused by the CT effect and to optimizing the analog synaptic behavior of the FeFET.

Peritoneal metastases from invasive lobular carcinoma (ILC) of breast are uncommon and usually related to poor prognosis due to difficulty of detection in clinical practice and drug resistance. Therefore, recognizing the entities of peritoneal metastases of ILC and the potential mechanism of drug resistance is of great significance for early detection and providing accurate management. We herein report a case of a 60-year-old female who presented with nausea and vomiting as the first manifestation after treated with abemaciclib (a CDK4/6 inhibitor) plus fulvestrant for 23 months due to bone metastasis of ILC. Exploratory laparotomy found multiple nodules in the peritoneum and omentum, and immunohistochemistry confirmed that the peritoneal metastatic lesions were consistent with ILC. Palliative therapy was initiated, but the patient died two months later due to disease progression with malignant ascites. Whole exome sequencing (WES) was used to detect the tumor samples and showed the peritoneal metastatic lesions had acquired ESR1 and PI3KCA mutations, potentially explaining the mechanism of endocrine therapy resistance. We argue that early diagnosis of peritoneal metastasis from breast cancer is crucial for prompt and adequate treatment and WES might be an effective supplementary technique for detection of potential gene mutations and providing accurate treatment for metastatic breast cancer patients.

Abstract Background The aim of this study was to evaluate the clinical outcome of autotransplantation of mature third molars to fresh molar extraction sockets using 3D replicas. Methods Ten patients underwent teeth autotransplantation with or without GBR. We observed the mobility, percussion, radiography examination, the probing depth and the masticatory function of the transplanted teeth during 2 years following up, which were transplanted into fresh molar sockets by using 3D replicas, and GBR when it is necessary. Results The average extra-oral time of donor tooth had been shortened to 1.65 min when used the 3D replica. Some probing depth of the transplanted tooth were deeper than 3 mm at 4 or 5 weeks temporarily. And one patient felt slight sensitive when chewing with soft food at 4 weeks, then disappeared. The clinical examination of the autotransplantation teeth during 1 year follow-up showed no sign of failure. Conclusions The tooth autotransplantation using 3D replica with or without GBR is an effective method which can reduce the extra-oral time of the donor teeth and may result in less failure.

Lead-free piezoelectric 0.92(K0.445Na0.5Li0.05)NbO3-0.08BaZrO3 (KNLN-BZ) ceramics were prepared via conventional sintering. Single-step, 2-step and 3-step temperature-controlled conditions were designed. The structure and electrical properties of ceramics obtained using different temperature-controlled procedures were systematically studied. It was found that ceramic prepared using the 3-step method with a holding time of 20 h showed the highest electrical properties. The Curie temperature was approximately 286 °C, and the dielectric constant and dielectric loss at room temperature were 1350 and 4.5% at the frequency of 1 kHz, respectively. The highest remanent polarization, piezoelectric strain and piezoelectric coefficient, d33*, were obtained 60 °C, indicating a phase transition between ferroelectric phases. Although the ceramics did not show excellent piezoelectric properties, the 3-step sintering method can be considered an effective method to optimize the electrical performances of KNN-based ceramics. Combined with an appropriate composition, ceramics with excellent electrical properties could be obtained. This study provides a path to enhance the density and electrical properties for KNN-based ceramics with simple composition and potential for industry application.

Background: Breast cancers can be divided into HER2-negative and HER2-positive subtypes according to different status of HER2 gene. Despite extensive studies connecting germline mutations with possible risk of HER2-negative breast cancer, the main category of breast cancer, it remains challenging to obtain accurate risk assessment and to understand the potential underlying mechanisms. Methods: We developed a novel framework named Damage Assessment of Genomic Mutations (DAGM), which projects rare coding mutations and gene expressions into Activity Profiles of Signalling Pathways (APSPs). Findings: We characterized and validated DAGM framework at multiple levels. Based on an input of germline rare coding mutations, we obtained the corresponding APSP spectrum to calculate the APSP risk score, which was capable of distinguish HER2-negative from HER2-positive cases. These findings were validated using breast cancer data from TCGA (AUC = 0.7). DAGM revealed that HER2 signalling pathway was up-regulated in germline of HER2-negative patients, and those with high APSP risk scores had exhibited immune suppression. These findings were validated using RNA sequencing, phosphoproteome analysis, and CyTOF. Moreover, using germline mutations, DAGM could evaluate the risk for HER2-negative breast cancer, not only in women carrying BRCA1/2 mutations, but also in those without known disease-associated mutations. Interpretation: The DAGM can facilitate the screening of subjects at high risk of HER2-negative breast cancer for primary prevention. This study also provides new insights into the potential mechanisms of developing HER2-negative breast cancer. The DAGM has the potential to be applied in the prevention, diagnosis, and treatment of HER2-negative breast cancer. Funding: This work was supported by the National Key Research and Development Program of China (grant no. 2018YFC0910406 and 2018AAA0103302 to CZ); the National Natural Science Foundation of China (grant no. 81202076 and 82072939 to MY, 81871513 to KW); the Guangzhou Science and Technology Program key projects (grant no. 2014J2200007 to MY, 202002030236 to KW); the National Key R&D Program of China (grant no. 2017YFC1309100 to CL); Shenzhen Science and Technology Planning Project (grant no. JCYJ20170817095211560 574 to YN); and the Natural Science Foundation of Guangdong Province (grant no. 2017A030313882 to KW and S2013010012048 to MY); Hefei National Laboratory for Physical Sciences at the Microscale (grant no. KF2020009 to GN); and RGC General Research Fund (grant no. 17114519 to YQS).

Field effect transistors (FETs) using two-dimensional molybdenum disulfide (MoS2) as the channel material has been considered one of the most potential candidates for future complementary metal-oxide-semiconductor technology with low power consumption. However, the understanding of the correlation between the device performance and material properties, particularly for devices with scaling-down channel lengths, is still insufficient. We report in this paper back-gate FETs with chemical-vapor-deposition grown and transferred MoS2 and Zr doped HfO2 ((Hf,Zr)O2, HZO) high-k dielectric gates with channel lengths ranging from 10 to 30 µm with a step of 5 µm. It has been demonstrated that channels with the length to width ratio of 0.2 lead to the most superior performance of the FETs. The MoS2/HZO hybrid FETs show a stable threshold voltage of ∼1.5 V, current on/off ratio of >104, and field effect mobility in excess of 0.38 cm2 V−1 s−1. The impact of the channel lengths on FET performance is analyzed and discussed in depth. A hysteresis loop has been observed in the Ids − Vgs characteristics of the hybrid FETs, which has been further studied and attributed to the charge effect at the interfaces. The HZO films show a relatively weak ferroelectric orthorhombic phase and thus serve mainly as the high-k dielectric gate. Charge trapping in the HZO layer that might induce hysteresis has been discussed. Our results show that MoS2/HZO hybrid FETs possess great potential in future low power and high-speed integrated circuits, and future work will focus on further improvement of the transistor performances using ferroelectric HZO films and the study of devices with even shorter MoS2 channels.

miR-101–3p may play a therapeutic role in various tumours. However, its anti-tumour mechanism remains unclear, and a definitive strategy to treat tumour cells in vivo is lacking. The objective of this study was to investigate the inhibitory mechanism of miR-101–3p on tumour cells and to develop relevant nanomedicines for in vivo therapy. The expression levels of miR-101–3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101–3p negatively correlated with clinical tumour size and TNM stage. miR-101–3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. We developed nanomedicine that can deliver miR-101–3p to tumour cells in vivo to achieve ferroptosis recovery, as well as to inhibit in vivo tumour proliferation. The miR-101–3p/TBLR1 axis plays an important role in tumour ferroptosis. Nanopharmaceuticals that increase miR-101–3p levels may be effective therapies to inhibit tumour proliferation.

Abstract Supra‐maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM‐specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800‐BBN) targets the gastrin‐releasing peptide receptor, and evaluated the image‐guided resection efficiency, sensitivity, specificity, and survivability. Twenty‐nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800‐BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6–100%). Eighty‐nine samples were harvested, including 70 fluorescence‐positive and 19 fluorescence‐negative samples. The sensitivity and specificity of IRDye800‐BBN were 94.44% (95% CI, 85.65–98.21%) and 88.24% (95% CI, 62.25–97.94%), respectively. Twenty‐five patients were followed up (median, 13.5 [3.1–36.0] months), and 14 had died. The mean preoperative and immediate and 6‐month postoperative Karnofsky performance scores were 77.9 ± 11.8, 71.3 ± 19.2, and 82.6 ± 14.7, respectively. The median overall and progression‐free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM‐specific fluorescent IRDye800‐BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.

Background: Gene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery. Methods: Using a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs’ vagina, which were made up of poly (β-amino ester) (PBAE)-plasmid polyplex nanoparticles (NPs) based two gel materials, modified montmorillonite (mMMT) and hectorite (HTT). Findings: By conducting flow cytometry of the cervical cells, we found that PBAE-GFP-NPs-mMMT gel was more efficient than PBAE-GFP-NPs-HTT gel in delivering exogenous DNA intravaginally. Next, we designed specific CRISPR/SpCas9 sgRNAs targeting porcine endogenous retroviruses (PERVs) and evaluated the genome editing efficacy in vivo. We discovered that PERV copy number in vaginal epithelium could be significantly reduced by the local delivery of the PBAE-SpCas9/sgRNA NPs-mMMT gel. Comparable genome editing results were also obtained by high-fidelity version of SpCas9, SpCas9-HF1 and eSpCas9, in the mMMT gel. Further, we confirmed that the expression of topically delivered SpCas9 was limited to the vagina/cervix and did not diffuse to nearby organs, which was relatively safe with low toxicity. Interpretation: Our data suggested that the PBAE-NPs mMMT vaginal gel is an effective preparation for local gene therapy, yielding insights into novel therapeutic approaches to sexually transmitted disease in the genital tract. Funding: This work was supported by the National Science and Technology Major Project of the Ministry of science and technology of China (No. 2018ZX10301402); the National Natural Science Foundation of China (81761148025, 81871473 and 81402158); Guangzhou Science and Technology Programme (No. 201704020093); National Ten Thousand Plan-Young Top Talents of China, Fundamental Research Funds for the Central Universities (17ykzd15 and 19ykyjs07); Three Big Constructions—Supercomputing Application Cultivation Projects sponsored by National Supercomputer Center In Guangzhou; the National Research FFoundation (NRF) South Africa under BRICS Multilateral Joint Call for Proposals; grant 17–54–80078 from the Russian Foundation for Basic Research.

The HfO2-based resistive random access memory (RRAM) is one of the most promising candidates for non-volatile memory applications. The detection and examination of the dynamic behavior of oxygen ions/vacancies are crucial to deeply understand the microscopic physical nature of the resistive switching (RS) behavior. By using synchrotron radiation based, non-destructive and bulk-sensitive hard X-ray photoelectron spectroscopy (HAXPES), we demonstrate an operando diagnostic detection of the oxygen ‘breathing’ behavior at the oxide/metal interface, namely, oxygen migration between HfO2 and TiN during different RS periods. The results highlight the significance of oxide/metal interfaces in RRAM, even in filament-type devices.

Background/Aims: Monitoring the appearance and progression of tumors are important for improving the survival rate of patients with ovarian cancer. This study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer (EOC) patients to evaluate their clinical significance in comparison to the existing biomarker CA125. Methods: Immuomagnetic bead screening, targeting epithelial antigens on ovarian cancer cells, combined with multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and CA125 were measured in serial from 153 blood and 153 serum samples from 51 patients and correlations with treatment were analyzed. Immunohistochemistry was used to detect the expression of tumor-associated proteins in tumor tissues and compared with gene expression in CTCs from patients. Results: CTCs were detected in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB disease had a CTC positive rate of 93% (13/14), much higher than the CA125 positive rate of only 64% (9/14) for the same patients. The numbers of CTCs changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035) in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in CTCs before treatment was also correlated with overall survival (OS) (p=0.041). Conclusion: Detection of CTCs allows early diagnose and expression of EpCAM in CTC positive patients predicts prognosis and should be helpful for monitoring treatment.

Acoustic tweezers for microparticle non-contact manipulation have attracted attention in the biomedical engineering field. The key components of acoustic tweezers are piezoelectric materials, which convert electrical energy to mechanical energy. The most widely used piezoelectric materials are lead-based materials. Because of the requirement of environmental protection, lead-free piezoelectric materials have been widely researched in past years. In our previous work, textured lead-free (K, Na)NbO3 (KNN)-based piezoelectric ceramics with high piezoelectric performance were prepared. In addition, the acoustic impedance of the KNN-based ceramics is lower than that of lead-based materials. The low acoustic impedance could improve the transmission efficiency of the mechanical energy between acoustic tweezers and water. In this work, acoustic tweezers were prepared to fill the gap between lead-free piezoelectric materials research and applications. The tweezers achieved 13 MHz center frequency and 89% −6 dB bandwidth. The −6 dB lateral and axial resolution of the tweezers were 195 μm and 114 μm, respectively. Furthermore, the map of acoustic pressure measurement and acoustic radiation calculation for the tweezers supported the trapping behavior for 100 μm diameter polystyrene microspheres. Moreover, the trapping and manipulation of the microspheres was achieved. These results suggest that the KNN-based acoustic tweezers have a great potential for further applications.

Abstract Background Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. Methods SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR. WST-1 assay was used to measure cell viability; the xeno-graft tumor model were used for in vivo study. RNA sequencing was analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling was accomplished with luciferase assays, real-time RT-PCR and Western blotting. Protein stability assay and ubiquitin assay was used to detect ER alpha protein degradation. Immuno-precipitation based assays were used to detect the interaction domain between ER alpha and SMURF1. The ubiquitin-based Immuno-precipitation based assays were used to detect the specific ubiquitination manner happened on ER alpha. Results Here, we identify the E3 ligase SMURF1 facilitates ER alpha signaling. We show that depletion SMURF1 decreases ER alpha positive cell proliferation in vitro and in vivo. SMURF1 depletion based RNA-sequence data shows SMURF1 is necessary for ER alpha target gene expression in the transcriptomic scale. Immunoprecipitation indicates that SMURF1 associates with the N-terminal of ER alpha in the cytoplasm via its HECT domain. SMURF1 increases ER alpha stability, possibly by inhibiting K48-specific poly-ubiquitination process on ER alpha protein. Interestingly, SMURF1 expression could be induced via estradiol treatment. Conclusions Our study reveals a novel positive feedback between SMURF1 and ER alpha signaling in supporting breast cancer growth. Targeting SMURF1 could be one promising strategy for ER alpha positive breast cancer treatment.

Objective: To evaluate obstetric outcomes in twin pregnancies of advanced maternal age (≥35 years). Materials and methods: A retrospective study involved 470 twin pregnancies in a single center from Sep. 1, 2012 to Mar. 31, 2015. Clinical characteristics and obstetric outcomes were recorded and compared among twin pregnancies who were classified as follows: age 20–29, 30–34, 35–39 and ≥40 years. Results: The incidence of gestational diabetes (age 20–29 years 15.8%; 30–34 years 24.3%; 35–39 years 30.4%; ≥40 years 57.1%; p = 0.004) and premature delivery (20–29 years 58.6%; 30–34 years 69.1%; 35–39 years 72.2%; ≥40 years 85.7%; p = 0.001) significantly increased with increasing age whereas spontaneous abortion (20–29 years 27.6%; 30–34 years 11.6%; 35–39 years 11.4%; ≥40 years 0.0%; p = 0.021) decreased in twin pregnancies of advanced maternal age. In addition, the rate of postpartum hemorrhage increased almost continuously by age and advanced maternal age was described as a risk factor for postpartum hemorrhage (age 35–39, adjusted OR 3.377; 95% confidence interval 1729–6.598; p

Albumin conjugates can enhance drug delivery. Here, the authors repurpose albumin-binding Evans blue to develop nanovaccines that co-deliver adjuvants and tumor neoantigens to antigen-presenting cells in lymph nodes, resulting in potent and durable antitumour immunity in combination immunotherapy.