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Histopathology image analysis plays a crucial role in cancer diagnosis. However, training a clinically applicable segmentation algorithm requires pathologists to engage in labor‐intensive labeling. In contrast, weakly supervised learning methods, which only require coarse‐grained labels at the image level, can significantly reduce the labeling efforts. Unfortunately, while these methods perform reasonably well in slide‐level prediction, their ability to locate cancerous regions, which is essential for many clinical applications, remains unsatisfactory. Previously, CAMEL is proposed, which achieves comparable results to those of fully supervised baselines in pixel‐level segmentation. However, CAMEL requires 1280 × 1280 image‐level binary annotations for positive WSIs. Here, CAMEL2 is presented, by introducing a threshold of the cancerous ratio for positive bags, it allows one to better utilize the information, consequently enabling us to scale up the image‐level setting from 1280 × 1280 to 5120 × 5120 while maintaining accuracy. The results with various datasets demonstrate that CAMEL2, with the help of 5120 × 5120 image‐level binary annotations, which are easy to annotate, achieves comparable performance to that of a fully supervised baseline in both instance‐ and slide‐level classifications.

Abstract Our current knowledge regarding the distribution patterns of ancient and recent recycled materials, as well as the origin of intraplate basalts in the eastern Asia Big Mantle Wedge (BMW), is limited. To address this, we conducted a detailed geochemical analysis of olivine melt inclusions (OLMI) in nephelinite samples. The normal OLMIs detected in our investigation exhibit geochemical features that closely resemble those of the hosting nephelinite, indicating a consistent association with a carbonated mantle source. Additionally, we identified a distinct group of anomalous OLMIs that displayed different geochemical characteristics from the hosting nephelinite but showed similarities to regional alkali basalts sourced from pyroxenite. The observed geochemical diversity in the nephelinite OLMIs suggests an interaction between deeply derived carbonated melts originating from the flattened Pacific slab in the mantle transition zone and pyroxenite in the lithospheric mantle. Carbonated fluid‐fluxed melting is key to basalt formation in the BMW.

Abstract The integration of electrochromic devices and energy storage systems in wearable electronics is highly desirable yet challenging, because self‐powered electrochromic devices often require an open system design for continuous replenishment of the strong oxidants to enable the coloring/bleaching processes. A self‐powered electrochromic device has been developed with a close configuration by integrating a Zn/MnO2 ionic battery into the Prussian blue (PB)‐based electrochromic system. Zn and MnO2 electrodes, as dual shared electrodes, the former one can reduce the PB electrode to the Prussian white (PW) electrode and serves as the anode in the battery; the latter electrode can oxidize the PW electrode to its initial state and acts as the cathode in the battery. The bleaching/coloring processes are driven by the gradient potential between Zn/PB and PW/MnO2 electrodes. The as‐prepared Zn||PB||MnO2 system demonstrates superior electrochromic performance, including excellent optical contrast (80.6%), fast self‐bleaching/coloring speed (2.0/3.2 s for bleaching/coloring), and long‐term self‐powered electrochromic cycles. An air‐working Zn||PB||MnO2 device is also developed with a 70.3% optical contrast, fast switching speed (2.2/4.8 s for bleaching/coloring), and over 80 self‐bleaching/coloring cycles. Furthermore, the closed nature enables the fabrication of various flexible electrochromic devices, exhibiting great potentials for the next‐generation wearable electrochromic devices.

Abstract In the context of rare but high‐impact extreme scenarios, such as natural disasters, it is crucial to utilize all available resources, including microgrids and distributed power sources, to restore critical loads in the distribution network as much as possible. This paper proposes a two‐stage resilience enhancement strategy for distribution networks considering post‐disaster topology reconstruction and demand response, aiming to facilitate the recovery of critical loads after disasters. In the first stage, a heuristic algorithm is introduced to determine the post‐disaster topology of the distribution network. In the second stage, by employing a step‐wise elastic load curve, user demand response is incorporated to maximize the socio‐economic value of the restoration, and resilience metrics are computed. Finally, the effectiveness of the proposed resilience restoration strategy is validated through simulations on Case33 and Case69 systems.

Abstract INTRODUCTION The development and progression of Alzheimer's disease (AD) is a complex process, during which genetic influences on phenotypes may also change. Incorporating longitudinal phenotypes in genome‐wide association studies (GWAS) could unmask these genetic loci. METHODS We conducted a longitudinal GWAS using a varying coefficient test to identify age‐dependent single nucleotide polymorphisms (SNPs) in AD. Data from 1877 Alzheimer's Neuroimaging Data Initiative participants, including impairment status and amyloid positron emission tomography (PET) scan standardized uptake value ratio (SUVR) scores, were analyzed using a retrospective varying coefficient mixed model association test (RVMMAT). RESULTS RVMMAT identified 244 SNPs with significant time‐varying effects on AD impairment status, with 12 SNPs on chromosome 19 validated using National Alzheimer's Coordinating Center data. Age‐stratified analyses showed these SNPs’ effects peaked between 70 and 80 years. Additionally, 73 SNPs were linked to longitudinal amyloid accumulation changes. Pathway analyses implicated immune and neuroinflammation‐related disruptions. DISCUSSION Our findings demonstrate that longitudinal GWAS models can uncover time‐varying genetic signals in AD. Highlights Identify time‐varying genetic effects using a longitudinal GWAS model in AD. Illustrate age‐dependent genetic effects on both diagnoses and amyloid accumulation. Replicate time‐varying effect of APOE in a second dataset.

Abstract The increase in initial Hf isotopes identified in early Mesoarchean detrital zircon is commonly interpreted as a reflection of the geodynamic transition from stagnant‐lid to mobile‐lid tectonics. However, given the lack of petrogenetic context, interpreting detrital zircon may lead to spurious conclusions. In this contribution, we use zircon U‐Pb‐Hf‐O isotopic and bulk rock compositions of newly identified 3.05–2.9 Ga granitoids from the SW Yangtze Block to posit petrogenesis within an isotopically juvenile magmatic system. A statistical analysis of these data with a global igneous zircon Lu‐Hf isotopic compilation reveals an increase in average initial radiogenic Hf isotopes during the Paleoarchean to Mesoarchean transition. We posit that the Earth's continental crust underwent a global rejuvenation across the Paleo‐Mesoarchean transition. This rejuvenation can be explained by an independently observed increase in mantle temperatures resulting from mantle thermal evolution and does not require a change in tectonic style.

Abstract Whether Mn carbonates can be used as a proxy for the oxygenation event is debated. Here we examined the Early Cretaceous lacustrine Mn carbonates from North China, which contain abundant microbial fossils. The extremely positive δ13C (up to +15‰ relative to Vienna Peedee belemnite) and micro‐area enrichment of Ni strongly indicate a methanogenic archaea origin of these microorganisms. Transmission electron microscope and electron energy loss spectroscopy show the nanoscale transformation of Mn‐oxides (Mg‐exchanged phyllomanganate) to Mn carbonates (kutnohorite), on extracellular polymeric substances. The reaction of the Mn oxides with organic matter resulted in increasing pH and alkalinity, together with the fluctuating pH, offering a suitable micro‐environment for the transformation processes. These Mn carbonates are therefore indicative of an oxidized, sulfate‐absent environment. The depicted scenario serves as a reference to ocean of the early Earth and provides a referable Mn oxide tracer for determining the emergence of the Great Oxidation Event.

Abstract Biological macromolecules exhibit emergent functions through hierarchical self‐assembly, a concept that is extended to design artificial supramolecular assemblies. Here, the first example of breaking the common parallel arrangement of capsule‐shaped zirconium coordination cages is reported by constructing the hierarchical porous framework ZrR‐1. ZrR‐1 adopts a quaternary structure resembling protein and contains 12‐connected chloride clusters, representing the highest connectivity for zirconium‐based cages reported thus far. Compared to the parallel framework ZrR‐2, ZrR‐1 demonstrated enhanced stability in acidic aqueous solutions and a tenfold increase in BET surface area (879 m2 g−1). ZrR‐1 also exhibits excellent proton conductivity, reaching 1.31 × 10−2 S·cm−1 at 353 K and 98% relative humidity, with a low activation energy of 0.143 eV. This finding provides insights into controlling the hierarchical self‐assembly of metal–organic cages to discover superstructures with emergent properties.

Abstract Myocardial ischemia–reperfusion injury (MIRI) was often observed after surgeries, causing a lot of suffering to patients. Inflammation and apoptosis were critical determinants during MIRI. We conveyed experiments to reveal the regulatory functions of circHECTD1 in MIRI development. The Rat MIRI model was established and determined by 2,3,5‐triphenyl tetrazolium chloride (TTC) staining. We analyzed cell apoptosis using TUNEL and flow cytometry. Proteins expression was evaluated by western blot. The RNA level was determined by qRT‐PCR. Secreted inflammatory factors were analyzed by ELISA assay. To predict the interaction sequences on circHECTD1, miR‐138‐5p, and ROCK2, bioinformatics analysis was performed. Dual‐luciferase assay was used to confirm these interaction sequences. CircHECTD1 and ROCK2 were upregulated in the rat MIRI model, while miR‐138‐5p was decreased. CircHECTD1 knockdown alleviated H/R‐induced inflammation in H9c2 cells. Direct interaction and regulation of circHECTD1/miR‐138‐5p and miR‐138‐5p/ROCK2 were confirmed by dual‐luciferase assay. CircHECTD1 promoted H/R‐induced inflammation and cell apoptosis by inhibiting miR‐138‐5p. miR‐138‐5p alleviated H/R‐induced inflammation, while ectopic ROCK2 antagonized such effect of miR‐138‐5p. Our research suggested that the circHECTD1‐modulated miR‐138‐5p suppressing is responsible for ROCK2 activation during H/R‐induced inflammatory response, providing a novel insight into MIRI‐associated inflammation.

Abstract The Cascadia margin is an unusual subduction zone characterized by the downdip movement of young and thin oceanic plates, where mantle flow and intraslab deformation are still unclear. Here we present new anisotropic tomography of the Cascadia subduction zone, in which the hexagonal symmetry axis of anisotropy is tilting rather than horizontal or vertical as assumed in previous studies of seismic anisotropy. Subduction‐induced entrained and toroidal flows under the Cascadia margin are discriminated well by the spatial relationship between tilting‐axis anisotropy and slab geometry. The obliquely entrained flow is trapped in a narrow zone (

Abstract Battery safety has attracted considerable attention worldwide due to the rapid development of wearable electronics and the steady increase in the production and use of electric vehicles. As battery failures are often associated with mechanical‐thermal coupled behaviors, protective shielding materials with excellent mechanical robustness and flame‐retardant properties are highly desired to mitigate thermal runaway. However, most of the thermal insulating materials are not strong enough to protect batteries from mechanical abuse, which is one of the most critical scenarios with catastrophic consequences. Here, inspired by wood, we have developed an effective approach to engineer a hierarchical nanocomposite via self‐assembly of calcium silicate hydrate and polyvinyl alcohol polymer chains (referred as CSH wood). The versatile protective material CSH wood demonstrates an unprecedented combination of light weight (0.018 g cm−3), high stiffness (204 MPa in the axial direction), negative Poisson's ratio (−0.15), remarkable toughness (6.67 × 105 J m−3), superior thermal insulation (0.0204 W m−1 K−1 in the radial direction), and excellent fire retardancy (UL94‐V0). When applied as a protective cover or a protective layer within battery packages, the tough CSH wood can resist high‐impact load and block heat diffusion to block or delay the spread of fire, therefore significantly reducing the risk of property damage or bodily injuries caused by battery explosions. This work provides new pathways for fabricating advanced thermal insulating materials with large scalability and demonstrates great potential for the protection of electronic devices.

Abstract In subduction zones with slab‐slab interactions, the pattern of mantle convection is very complex and still unclear. In this study, we jointly invert a large number of P and S wave arrival time data of local earthquakes for 3‐D isotropic and anisotropic velocity structures of the Banda subduction zone. Along the curved Banda arc, the subducting Indo‐Australian slab is detected clearly as a high‐velocity zone, and its azimuthal anisotropy changes along the arc strike, representing fossil anisotropy within the slab and modified anisotropy by the subduction processes. Around the northern edge of the Banda slab, a semi‐toroidal pattern of anisotropy appears in low‐velocity anomalies, representing mantle flow extruded from the Banda arc and escaped from a gap of the Banda‐Molucca slab toward the northeast. Our 3‐D anisotropic tomography uncovers the mantle convection pattern induced by the slab‐slab interactions, shedding new light on the complex dynamical processes in this curved subduction zone.

Abstract Traditionally, longwall top coal caving (LTCC) panels adopt the single‐window drawing mode and their drawing efficiency is relatively low. The synchronous multi‐window drawing (SMWD) mode is a remarkable approach to resolve the incompatibility between shearer coal mining and top‐coal drawing. The present paper analyzes the caving characteristics of top coal under SMWD in LTCC mining of extra‐thick coal seam. The caving and migration of top‐coal fragments were simulated by using the continuum–discontinuum element method (CDEM). The results show that the SMWD mode can effectively improve the drawing smoothness with larger caving channels compared to the traditional single‐window drawing mode. The main caving channel for top‐coal fragments was directly above the assembled multi‐window (AMW), and the size of the AMW had a great influence on the distribution of the velocity field. Additionally, the simulated draw body of the initial drawing adopted an elliptical shape, which changed into a variation ellipse with the increasing size of the AMW. The boundary of the simulated draw body of the initial drawing presented an irregular shape that deviated from the results predicted by the Bergmark–Roos model. Furthermore, the drawing efficiency increased with the expansion of the AMW, whereas the recovery ratio first increased and then decreased with the expansion of the AMW. Finally, field tests revealed that the SMWD mode can greatly improve the drawing efficiency. Thus, the recovery ratio under A2 and A3 SMWD modes was higher than that of the traditional single‐window drawing mode. Based on the results of field tests and CDEM simulation, it is recommended to adopt A2 and A3 SMWD modes to enhance the top‐coal recovery ratio and drawing efficiency. These research results could constitute a technical reference for automated highly efficient top‐coal drawing and high‐yield LTCC panel extracting extra‐thick coal seam.

Abstract Background The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. Methods We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. Results This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. Conclusions Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.

Abstract The ankle‐link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness‐associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein‐coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits. Importantly, ADGRV1 inhibits WHRN phosphorylation through regional cAMP‐PKA signaling, which in turn regulates the ubiquitination and stability of USH2A via local signaling compartmentalization, whereas ADGRV1 Y6236fsX1 does not. Yeast two‐hybrid screening identified the E3 ligase WDSUB1 that binds to WHRN and regulates the ubiquitination of USH2A in a WHRN phosphorylation‐dependent manner. Further FlAsH‐BRET assay, NMR spectrometry, and mutagenesis analysis provided insights into the architectural organization of ALC and interaction motifs at single‐residue resolution. In conclusion, the present data suggest that ALC organization and accompanying local signal transduction play important roles in regulating the stability of the ALC.

Abstract Background This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. Method This study was a multicenter, randomized, open‐label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8‐week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: −1.0 g/dl) was tested between the two treatments. The time‐dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron‐binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results Four hundred and sixty‐six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per‐protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were −0.07 and −0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: −0.22 to 0.39), and the lower limit of the 95% CI was −0.22 > −1.0 g/dl. The average Hb concentrations of the two groups were 10.88–11.43 g/dl (darbepoetin alfa) and 10.91–11.38 g/dl (epoetin alfa) during the study period of Weeks 0–28, with the maintenance rates of the target Hb concentration ranging within 71%–87% and 78%–95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. Conclusion The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Abstract The East Kunlun Shan (EKLS) in northern Tibet occupies boundaries of the low‐relief topography and lower crustal low‐velocity zone in the interior plateau, making it ideal for exploring the relationship of surface deformation with underlying geodynamic processes. We used previous and new apatite (U‐Th)/He data to analyze the exhumation history and pattern throughout the EKLS and link surface deformation to deep structures. Integrated (U‐Th)/He ages reveal the rapid exhumation at 27–25 Ma, due to the coeval orogen‐scale tilting of the EKLS. Along with the crustal structures beneath the EKLS, it is inferred that orogen‐scale tilting is the isostatic response of the nonuniform crustal thickening related to northward injection of the Tibetan lower crust. This study highlights the role of ductile deformation within the lower crust in mountain building in northern Tibet, which shares a similarity with mountain building pattern in the eastern plateau margin.

Abstract Background Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0–12.0 g/dL) for the treatment of renal anemia. Methods Ninety‐five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18–70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA‐naive (erythropoiesis stimulating agent‐naive). The primary efficacy profile was the mean Hb level (the non‐inferiority margin was −1.0 g/dL, week 21–28); the secondary efficacy profiles were the Hb increase rate (week 0–4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>−1.0 g/dL), and non‐inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. Conclusion Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Diabetic wounds are serious complications caused by diabetes mellitus (DM), which are further exacerbated by angiogenesis disorders and prolonged inflammation. Injectable platelet-rich fibrin (i-PRF) is rich in growth factors (GFs) and has been used for the repair and regeneration of diabetic wounds; however, direct application of i-PRF has certain disadvantages, including the instability of the bioactive molecules. Sericin hydrogel, fabricated by silkworm-derived sericin, is a biocompatible material that has anti-inflammatory and healing-promoting properties. Therefore, in this study, we developed a novel hydrogel (named sericin/i-PRF hydrogel) using a simple one-step activation method. The in vitro studies showed that the rapid injectability of the sericin/i-PRF hydrogel allows it to adapt to the irregular shape of the wounds. Additionally, sericin hydrogel could prolong the release of i-PRF-derived bioactive GFs in the sericin/i-PRF hydrogel. Furthermore, sericin/i-PRF hydrogel effectively repaired diabetic wounds, promoted angiogenesis, and reduced inflammation levels in the diabetic wounds of nude mice. These results demonstrate that the sericin/i-PRF hydrogel is a promising agent for diabetic wound healing.

Background: Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified. Methods: The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann–Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal–Wallis test for multiple group comparisons. Results: Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P

Abstract Hydrogel actuators have shown great promise in underwater robotic applications as they can generate controllable shape transformations upon stimulation due to their ability to absorb and release water reversibly. Herein, a photoresponsive anisotropic hydrogel actuator is developed from poly(N‐isopropylacrylamide) (PNIPAM) and gold‐decorated carbon nitride (Au/g‐C3N4) nanoparticles. Carbon nitride nanoparticles endow hydrogel actuators with photocatalytic properties, while their reorientation and mobility driven by the electrical field provide anisotropic properties to the surrounding network. A variety of light‐fueled soft robotic functionalities including controllable and programmable shape‐change, gripping, and locomotion is elicited. A responsive flower‐like photocatalytic reactor is also fabricated, for water splitting, which maximizes its energy‐harvesting efficiency, that is, hydrogen generation rate of 1061.82 µmol g−1 h−1, and the apparent quantum yield of 8.55% at 400 nm, by facing its light‐receiving area adaptively towards the light. The synergy between photoactive and photocatalytic properties of this hydrogel portrays a new perspective for the design of underwater robotic and photocatalytic devices.

Abstract This paper studies trajectory tracking control problem of quadrotor in the presence of external disturbances. A new control scheme integrating adaptive sliding mode disturbance observer (ASMDO) with backstepping funnel control is designed in both position loop and attitude loop. Adaptive sliding mode disturbance observer is utilized to estimate and compensate the external disturbances of quadrotor system, which relaxed the upper bound requirement in conventional sliding mode disturbance observer (SMDO) whilst adapting the gain of discontinuous term to a level as small as possible for consideration of chattering mitigation. The modified funnel function not only guarantees the dynamic quality in the tracking process but also avoids derivative operation of Euclidian norm of tracking error in the backstepping design. To guarantee stabilization of closed‐loop system, Lyapunov stability criterion is utilized in the overall controller design process. Finally, the effectiveness and superiority of the proposed scheme are illustrated by simulation results.

Abstract The undesirable Li dendrite growth and other knock‐on issues have significantly plagued the application of Li metal anodes (LMAs). Herein, we report that the synergistic regulation of double interfaces adjacent to the metallic Li anode can effectively prevent the dendritic Li growth, significantly improving the cycling performance of LMAs under harsh conditions including high current density and high depth of discharge. Thorough comparison of electrolytes demonstrated that 1 M lithium bis(fluorosulfonyl)imide (LiFSI) in 1,2‐dimethoxyethane (DME) can yield a robust and lithiophobic LiF‐rich upper interface (solid electrolyte interphase). Besides, the Sb‐based buffer layer forms a lithiophilic lower interface on current collector. The synergy of the upper and lower interfacial engineering plays an important role for outstanding cyclability of LMAs. Consequently, the plating/stripping of Li can be stably repeated for 835 and 329 cycles with an average Coulombic efficiency (CE) above 99% at 1 and 3 mA h cm−2, respectively. Surprisingly, the Li||Li symmetric cell can even withstand the baptism of current density up to 20 mA cm−2. The excellent performance validates that the facile synergistic regulating of interfaces adjacent to the metallic Li anode provides an effective pathway to stabilize LMAs.

Abstract Aims/Introduction β‐Cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young‐onset type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos. Materials and Methods We injected one‐cell stage embryos with a dachb‐morpholino (MO) or with the dachb‐MO and dachb messenger ribonucleic acid, and determined the effect on the development of the pancreatic islet. We also carried out quantitative polymerase chain reaction and ribonucleic acid sequencing on the dachb‐MO group to determine the effect of dachb knockdown on gene expression. Results MO‐mediated dachb knockdown resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers. This islet developmental defect was rescued when embryos were co‐injected with dachb‐MO and dachb messenger ribonucleic acid. Knockdown of dachb was associated with a significant downregulation of the β‐cell specific marker gene, insa, and the somatostatin cell marker, sst2, as well as regulators of pancreas development, ptf1a, neuroD, pax6a and nkx6.1, and the cell cycle gene, insm1a. Furthermore, ribonucleic sequencing analysis showed an upregulation of genes enriched in the forkhead box O and mitogen‐activated protein kinase signaling pathways in the dachb‐MO group, when compared with the control groups. Conclusions Together, our results suggest the possible role of dachb in islet development in zebrafish.

Abstract Network pruning is a significant way to improve the practicability of convolution neural networks (CNNs) by removing the redundant structure of the network model. However, in most of the existing network pruning methods l1 or l2 regularisation is applied to parameter matrices and the manual selection of pruning threshold is difficult and labor‐intensive. A novel CNNs network pruning method via l0 regularisation is proposed, which adopts l0 regularisation to expand the saliency gap between neurons. A half‐quadratic splitting (HQS) based iterative algorithm is put forward to calculate the approximation solution of l0 regularisation, which makes the joint optimisation problem of regularisation term and training loss function can be solved by various gradient‐based algorithms. Meanwhile, a hyperparameters selection method is designed to make most of the hyperparameters in the algorithm can be determined by examining the pre‐trained model. The results of experiments on MNIST, Fashion‐MNIST and CIFAR100 show that the proposed method can provide a much clearer pruning threshold by widening the saliency gap, and achieve a similar or even better compression performance, compared with the state‐of‐the‐art studies.

Background Propofol has been reported to be related to the migration, invasion, and epithelial‐mesenchymal transition (EMT) of esophageal cancer (EC) cells. However, the detailed mechanism has not yet been fully reported. The purpose of this research was to elucidate the function of long non‐coding RNA TMPO antisense RNA 1 (lncRNA TMPO‐AS1) and microRNA‐498 (miR‐498) in propofol‐regulated EC. Methods Transwell assay was performed to assess cell migratory and invasive abilities. Western blot assay was employed to determine the levels of EMT markers and hypoxia inducible factor‐1 (HIF‐1α). Quantitative real‐time polymerase chain reaction (qRT‐PCR) was carried out to detect the levels of TMPO‐AS1 and miR‐498. Moreover, the interaction between TMPO‐AS1 and miR‐498 was predicted by starBase, and then confirmed by the dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results Propofol suppressed hypoxia‐induced EC cell migration, invasion, and EMT. Both TMPO‐AS1 overexpression and miR‐498 knockdown weakened the effect of propofol on hypoxia‐induced EC cell progression. Interestingly, TMPO‐AS1 targeted miR‐498 and suppressed miR‐498 expression. TMPO‐AS1 regulated EC cell progression via downregulating miR‐498 expression. Conclusions Collectively, our findings demonstrated that propofol inhibited hypoxia‐induced EC cell mobility through modulation of the TMPO‐AS1/miR‐498 axis, providing a theoretical basis for the treatment of EC.

Nanoribbons based on low-dimensional materials are potential candidates for nanoscale spintronics devices. Here, some ferromagnetic silicene nanoribbons with zigzag and Klein edges (N-ZKSiNRs) are constructed. It is demonstrated that the N-ZKSiNRs with various widths (N) are placed in various spin-resolved electronic situations. With the increase of the width parameter N from 4 to 19, the N-ZKSiNRs pass from the indirect-gap bipolar magnetic semiconducting state (BMS) to the bipolar spin-gapless semiconductor (BSGS) and eventually to half-metallicity (HM). Moreover, applying a temperature gradient through the nanoribbons leads to spin-dependent current with the opposite flowing and spin orientations, demonstrating the spin-dependent Seebeck effect (SDSE). Besides, it was found that the BSGS phase is superior to the BMS and HM for generating SDSE. These findings confirm that the ZKSiNRs are promising choices for spin caloritronics devices.

Spin caloritronic devices, as multifunctional devices, combining spintronics, and caloritronics, are essential for the sustainable development of humans. Here, a novel spin caloritronic device is presented using a diarylethene molecule photoswitch sandwiched among two semi-infinite zigzag graphene nanoribbons containing asymmetrical edge hydrogenation electrodes. We demonstrate that the temperature gradient between the right and the left electrodes can generate spin-up (SU) and spin-down (SD) currents moving in opposite orientations. Moreover, the mentioned currents possess approximately the same magnitudes, indicating a nearly nondissipative spin Seebeck effect. We also find that these currents are significantly dissimilar for the two photochromic isomers at different temperature gradients, demonstrating the excellent system’s switching nature. The obtained results reveal that the light can control the thermal spin transport properties.

Abstract The unique electronic structure and crystal structure driven by external pressure in transition metal tellurides (TMTs) can host unconventional quantum states. Here, the discovery of pressure‐induced phase transition at ≈2 GPa, and dome‐shaped superconducting phase emerged in van der Waals layered NbIrTe4 is reported. The highest critical temperature (Tc) is ≈5.8 K at pressure of ≈16 GPa, where the interlayered Te–Te covalent bonds form simultaneously derived from the synchrotron diffraction data, indicating the hosting structure of superconducting evolved from low‐pressure two‐dimensional (2D) phase to three‐dimensional (3D) structure with pressure higher than 30 GPa. Strikingly, the authors have found an anisotropic transport in the vicinity of the superconducting state, suggesting the emergence of a “stripe”‐like phase. The dome‐shaped superconducting phase and anisotropic transport are possibly due to the spatial modulation of interlayer Josephson coupling .

Abstract The Permian Emeishan large igneous province (LIP) in Southwestern China is recognized as a remnant of mantle plume activity. Its crust composition has a significant bearing on understanding the magmatic plumbing system in a LIP and the volume of magmas generated, which is critical to the viability of the mantle plume model and its potential environmental impact but is difficult to constrain. Here, a SiO2‐VP/VS‐VS relationship, compiled from existing laboratory measurements, is used to estimate the crustal SiO2 content of the Emeishan LIP based on the joint constraint of the crustal bulk VP/VS ratio and average VS. The crust underneath the northeastern inner zone of the Emeishan LIP has a SiO2 content of ∼55.7 wt%, in contrast with the bulk continental crust's SiO2 content of 62.1 ± 2.1 wt% but largely overlapping with the exposed mafic‐ultramafic intrusions. Such an unusually “mafic” crust is attributable to the intensive magmatic underplating and intraplating associated with the Emeishan mantle plume. It further allows a minimum estimate of the volume of ∼1.45 × 106 km3 for erupted magmas and ∼2.39 × 106 km3 for total emplaced magmas, which is comparable to the volume of typical plume‐generated LIPs.

Objective Wear‐induced aseptic loosening has been accepted as one of the main reasons for failure of total hip arthroplasty. Ceramic wear debris is generated following prosthesis implantation and plays an important part in the upregulation of inflammatory factors in total hip arthroplasty. The present study investigates the influence of ceramic debris on osteoblasts and inflammatory factors. Methods Ceramic debris was prepared by mechanical grinding of an aluminum femoral head and added to cultures of MC3T3‐E subclone 14 cells at different concentrations (i.e. 0, 5, 10, and 15 μg/mL). Cell proliferation was evaluated using a Cell Counting Kit (CCK‐8), and cell differentiation was assessed by mRNA expression of alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In addition, cell bio‐mineralization was evaluated through alizarin red S staining, and release of tumor necrosis factor alpha (TNF‐α), interleukin‐1 beta (IL‐1β), and interleukin‐6 (IL‐6) was measured through enzyme‐linked immunosorbent assays (ELISA). Furthermore, mRNA expression of Smad1, Smad4, and Smad5 and protein expression of phosphorylated Smad1, Smad4, and Smad5 were measured by reverse transcriptase polymerase chain reaction (RT‐PCR) and western blotting. Results The ceramic debris had irregular shapes and sizes, and analysis of the size distribution using a particle size analyzer indicated that approximately 90% of the ceramic debris was smaller than 3.2 μm (2.0 ± 0.4 μm), which is considered clinically relevant. The results for mRNA expression of ALP, OCN, and OPN and alizarin red S staining indicated that cell differentiation and bio‐mineralization were significantly inhibited by the presence of ceramic debris at all tested concentrations (P < 0.05, and the values decreased gradually with the increase of ceramic debris concentration), but the results of the CCK‐8 assay showed that cell proliferation was not significantly affected (P > 0.05; there was no significant difference between the groups at 1, 3, and 5 days). In addition, the results of ELISA, RT‐PCR, and western blotting demonstrated that ceramic debris significantly promoted the release of inflammatory factors, including TNF‐α, IL‐β, and IL‐6 (P < 0.05, and the values increased gradually with the increase of ceramic debris concentration), and also greatly reduced the mRNA expression of Smad1, Smad4, and Smad5 (the values decreased gradually with the increase of ceramic debris concentration) as well as protein expression of phosphorylated Smad1, Smad4, and Smad5. Conclusion Ceramic debris may affect differentiation and bio‐mineralization of MC3T3‐E subclone 14 cells through the bone morphogenetic protein/Smad signaling pathway.

The electronic structure of GaSe/silicane (GaSe/SiH) van der Waals (vdW) heterostructure in response to a vertical electric field and strain was studied via first-principle calculations. The heterostructure had indirect band gap characteristics in the range [−1.0, −0.4] V/Å and direct band gap features in the range [−0.3, 0.2] V/Å. Furthermore, a type-II to type-I band alignment transition appeared at −0.7 and −0.3 V/Å. Additionally, the GaSe/SiH vdW heterostructure had a type-II band alignment under strain, but an indirect to direct band gap semiconductor transition occurred at −3%. These results indicated that the GaSe/SiH vdW heterostructure may have applications in novel nanoelectronic and optoelectronic devices.

The interfacial transition zone (ITZ) is a weak region of recycled concrete. To further study the influence of the ITZ on the damage performance of recycled concrete, a formula for calculating the ITZ thickness is derived, and the ITZ thickness is calculated for various recycled concrete mixtures with a recycled aggregate content of 30%. The concrete model test method and finite element analysis software were used to numerically simulate common concrete and recycled concrete with ITZ thicknesses of 0.05 mm, 1 mm, 2 mm, 3 mm, and 4 mm. The results show that the thickness of the ITZ has an obvious influence on the cracking strength of recycled concrete and that the cracking strength of recycled concrete decreases with increasing ITZ thickness. The cracks in recycled concrete initiate from the ITZ, and the damage degree increases with increasing ITZ thickness. Compared with that of common concrete, the cracking strength of recycled concrete with an ITZ thickness of no more than 2 mm (i.e., the replacement rate of the recycled aggregates is no more than 30%) is not significantly reduced.

In recent years, much interest in the study of Van der Waals heterostructures (vdWhs) has arisen. This has led to a significant amount of fundamental research being produced, from which novel optoelectronic applications have been established. By using first principles, we analyze the electronic structure of silicane/SnSe2 vdWhs in the response to an externally applied electric field and a normal strain. The results show that the silicane/SnSe2 vdWh acts as an indirect semiconductor when it is subjected to an applied electric field between −1 and 0.1 V/Å and becomes a metal in the 0.2 to 1 V/Å range. Significantly, the electronic band alignments of the silicane/SnSe2 vdWhs are modified from a type-II to a type-I when a field of −0.7 V/Å is applied. Furthermore, it is determined that the silicane/SnSe2 vdWhs appears to have a semiconductor-metal phase transition at a strain of −5%. Our results indicate that the silicane/SnSe2 vdWhs have the potential for applications in novel high-performance optoelectronic devices.

With the development of mechatronic systems, different kinds of subsystems within them are highly correlated to each other due to the demand for the special function. To assess the robustness in the mechatronic system under various disturbances, we build an interdependent mechatronic system as an interdependent machine-electricity-communication network (IMECN) and adopt the improved cascading failure model where the occurrence of the failure propagation is decided by a proportion threshold δ. In order to fully explore the robustness under different disturbances, we develop attack strategies concerning nodes, edges, and interdependent links by considering measures for a node. Then, we also define the robustness metric to quantify the performance of IMECN during the entire attack process. The mass transit vehicle is taken as an example to investigate the impact of attack strategies on the robustness at different δ in a real-world mechatronic system. It is found that each subnetwork in this IMECN has a scale-free property. Based on simulation results, we obtain the most efficient attack strategies to remove nodes, edges, and interdependent links for different possibilities of triggering the failure propagation. In addition, we find that the attacks on nodes and interdependent links make IMECN more vulnerable compared with the ones on edges. This work provides theoretical insights into the comprehensive analysis of the robustness in interdependent mechatronic systems.

Background. Urinary kidney injury molecule 1 (uKIM-1) is a proximal tubular injury biomarker for predicting acute kidney injury (AKI); its prognostic value varies depending on the clinical and population characteristics. However, the predictive value of uKIM-1 for diagnosis of contrast-induced acute kidney injury (CI-AKI) remains unclear. Method. Medline, Embase, ClinicalTrials.gov, Cochrane Library database, and the China National Knowledge Infrastructure (CNKI) were used to identify relevant studies from their inception to November 31, 2019. Studies that met the inclusion criteria were included. Relevant data were extracted to obtain pooled sensitivity (SEN) and specificity (SPE), summary receiver operating characteristic curve (ROC), and area under the ROC (AUC or AUROC). A bivariate mixed-effects regression model was used for data analysis. Results. A total of 946 patients from 8 eligible studies were included. Across all the studies, the diagnostic odds ratio (DOR) for uKIM-1 level to predict CI-AKI was 19 (95% CI 10–39), with SEN and SPE of 0.84 and 0.78, respectively. The AUROC for uKIM-1 in predicting CI-AKI was 0.88 (95% CI 0.85–0.90). There was a substantial heterogeneity across the studies (I2 was 37.73% for the summary sensitivity and 69.31% for the summary specificity). Conclusion. Urinary KIM-1 has a high predictive value for diagnosis of CI-AKI in patients who have undergone cardiac catheterization.

Coupled matrix and tensor factorizations have been successfully used in many data fusion scenarios where datasets are assumed to be exactly coupled. However, in the real world, not all the datasets share the same factor matrices, which makes joint analysis of multiple heterogeneous sources challenging. For this reason, approximate coupling or partial coupling is widely used in real-world data fusion, with exact coupling as a special case of these techniques. However, to fully address the challenge of tensor factorization, in this paper, we propose two improved coupled tensor factorization methods: one for approximately coupled datasets and the other for partially coupled datasets. A series of experiments using both simulated data and three real-world datasets demonstrate the improved accuracy of these approaches over existing baselines. In particular, when experiments on MRI data is conducted, the performance of our method is improved even by 12.47% in terms of accuracy compared with traditional methods.