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High-field strain and its temperature stability of (1–x) K0.48Na0.52Nb0.96Ta0.04O3-xBaZrO3+8%MnO+3%ZrO2 (in mole, KNNT-xBZ+8Mn) ceramics sintered in reducing atmosphere are improved simultaneously via defect design in A and B site. There is a conducting type transition from n-type to p-type at x = 0.07. The BaZrO3 dopant not only induces the increase of defects (ZrNb′, BaNa·, BaK·) concentration, but also results in the increase of defect (MnNb‴) concentration, because more Mn ions as +2 oxidation state in ceramics is triggered by BaZrO3 doping modification. Defect dipoles (MnNb′′′−Vo··, ZrNb′-Vo··, BaNa·-VNa′, BaK·-VK′) in poled and aged ceramics enhance the reversibility of the non–180° domains switching, which increases the high-field strain of KNNT-xBZ+8Mn ceramics. The reversibility of non–180° domain switching can be preserved to high temperature due to stable defect dipoles (BaNa·-VNa′, BaK·-VK′) in A-site. The KNNT-xBZ+8Mn ceramics at x = 0.07 show the largest high-field strain coefficient (543 pm/V@20 kV/cm) and the highest temperature stability (125 °C). The KNNT-xBZ+8Mn ceramic is a lead-free material with great potential to be applied in the fabrication of multilayer ceramic actuators with Ni inner electrodes in the future.

Abstract Studies on the piezoelectric materials capable of efficiently outputting high electrostrains at low electric fields are driven by the demand for precise actuation in a wide range of applications. Large electrostrains of piezoceramics in operation require high driving fields, which limits their practical application due to undesirable nonlinearities and high energy consumption. Herein, a strategy is developed to enhance the electrostrains of piezoceramics while maintaining low hysteresis by incorporating lead magnesium niobate relaxors into lead zirconate titanium at the morphotropic phase boundary. An ultrahigh inverse piezoelectric coefficient $${d}_{33}^{*}$$ d 33 * of 1380 pm/V with a reduced hysteresis of 11.5% is achieved under a low electric field of 1 kV/mm, outperforming the major lead-based piezoelectric materials. In situ synchrotron X-ray diffraction and domain wall dynamics characterization with sub-microsecond temporal resolution reveal that the outstanding performances originate from facilitated domain wall movement, which in turn is due to reduced lattice distortion and miniaturized domain structures. These findings not only address the pending challenges of effective actuation under reduced driving conditions but also lay the foundation for a more systematic approach to exploring the origin of large electrostrains.

Abstract Gynecologic cancers develop from the female reproductive organs. Microbial dysbiosis in the gut and oral cavity can communicate with each other through various ways, leading to mucosal destruction, inflammatory response, genomic instability, and ultimately inducing cancer and worsening. Here, we introduce the mechanisms of interactions between gut and oral microbiota and their changes in the development of gynecologic tumors. In addition, new therapeutic approaches based on microbiota modulation are discussed.

Abstract Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Abstract Chronic obstructive pulmonary disease(COPD) is a gradually worsening and fatal heterogeneous lung disease characterized by airflow limitation and increasingly decline in lung function. Currently, it is one of the leading causes of death worldwide. The consistent feature of COPD is airway inflammation. Several inflammatory factors are known to be involved in COPD pathogenesis; however, anti-inflammatory therapy is not the first-line treatment for COPD. Although bronchodilators, corticosteroids and roflumilast could improve airflow and control symptoms, they could not reverse the disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway plays an important novel role in the immune system and has been confirmed to be a key mediator of inflammation during infection, cellular stress, and tissue damage. Recent studies have emphasized that abnormal activation of cGAS-STING contributes to COPD, providing a direction for new treatments that we urgently need to develop. Here, we focused on the cGAS-STING pathway, providing insight into its molecular mechanism and summarizing the current knowledge on the role of the cGAS-STING pathway in COPD. Moreover, we explored antagonists of cGAS and STING to identify potential therapeutic strategies for COPD that target the cGAS-STING pathway.

Abstract In this work, we realized the detection of diamino-pentazolium cation (DAPZ+) in the reaction solution experimentally and proved it to be meta-diamino-pentazole based on the transition state theory. Quantum chemical methods were used to predict its spectral properties, charge distribution, stability and aromaticity. Considering that DAPZ+ has excellent detonation properties, it was further explored by assembling it with N5 −, N3 − and C(NO2)3 − anions, respectively. The results show a strong interaction between DAPZ+ and the three anions, which will have a positive effect on its stability. Thanks to the high enthalpy of formation and density, the calculated detonation properties of the three systems are exciting, especially [DAPZ+][N5 −] (D: 10,016 m·s−1; P: 37.94 GPa), whose actual detonation velocity may very likely exceed CL-20 (D: 9773 m·s−1). There is no doubt that this work will become the precursor for the theoretical exploration of new polynitrogen ionic compounds.

Abstract Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/β-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/β-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-β estradiol group (E2: 25 µg /kg/d 17β-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, β-catenin, LRP5, RUNX2 and OPG of the Wnt/β-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/β-catenin signaling pathway.

Abstract Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium–sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal–orthorhombic–rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

Abstract Because of its high energy, aromaticity, and carbon- and hydrogen-free structure, the cyclo-pentazolate anion (c-N5 -) has attracted increased attention as a potential polynitrogen structural unit for the research of next-generation high energy density materials. However, the poor thermal stability of c-N5 --based compounds has become an important factor restricting their development. Here, we show that a hydrogen-bonded organic framework (HOF) self-assembles with and stabilizes c-N5 -, with c-N5 - situated in the pores of the resulting framework through the formation of symmetrical c-N5 - hydrogen bonds as the main stabilizing factors. These factors result in an onset decomposition temperature of 153 °C for the c-N5 -@HOF portion, which exceeds the thermal stabilities generally observed for c-N5 --based derivatives of below 135 °C. We envisage that further c-N5 --based materials with enhanced stabilities and better performance will be developed in the future.

Abstract Wireless and battery-free radio-frequency (RF) sensors can be used to create physical spaces that ambiently sense and respond to human activities. Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments, accommodate daily activities, and functionally integrate with objects. However, existing RF sensors are unable to simultaneously achieve high transparency, flexibility, and the electrical conductivity required for remote room-scale operation. Here, we report 4.5 µm RF tag sensors achieving transparency exceeding 90% that provide capabilities in room-scale ambient wireless sensing. We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale. By individually tagging multiple objects and regions of the human body, we demonstrate multiplexed wireless tracking of human-environment interactions and physiological signals at a range of up to 8 m. These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.

Abstract Background Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae. Methods In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested. Results Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1β (Il-1β), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria. Conclusions Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.

As an important intermediate in the synthesis of most energetic pentazole compounds, the reaction system of sodium pentazole is complex and has many by-products, but there is no suitable HPLC analysis method. Based on the study of ultraviolet absorption peak of sodium pentazole aqueous solution, the HPLC purity analysis method of sodium pentazole was successfully established and its sensitivity, accuracy and repeatability were verified. When the detection wavelength was 192 nm, the chromatographic column was Agilent WondaSil C18 Superb (4.6 × 250 mm, 5 μm), the mobile phase was 95% water and 5% acetonitrile mixed solution, the flow rate was 0.8 ml/min, the analysis time was 8 min, the sample size was 1 μL and the column temperature was 40 °C, a liquid phase map of sodium pentazole was obtained. The analysis results showed that the retention time of pentazole sodium was 3.76 min, and showed a good linear relationship in the range of 0.3068–0.3288 g/L. The linear equation is y = -217447.64+835837.85x, the correlation coefficient R2 is 0.99997, and it has good sensitivity, accuracy and repeatability. In addition, three by-products from the synthesis of sodium pentazole were simply separated.

This study was conducted to investigate the impact of EGCG on antioxidant stress, immune response, and intestinal microbiota flora in post-weaning rabbits. A total of 144 40 d Ira rabbits (equally divided by sex), were randomly allocated to six treatments. with five groups receiving doses of 200, 400, 600, 800, and 1000 mg/kg of EGCG, while one group served as a control without EGCG. Over 48 days, this study the assessed growth performance, antioxidant capacity, immune system, intestinal morphology, and cecal microbiota in the rabbits. The results showed that EGCG did not affect growth performance; however, significant linear and quadratic correlations were observed between the MDA, T-AOC, and GSH-Px activities in the liver and jejunum (p < 0.05). Quadratic effects were observed for the spleen and thymus indexes and serum IgG levels with increasing EGCG dosages (p < 0.05). Additionally, positive linear and quadratic effects were found on the ileal villus height and the villus height/crypt depth ratio. The relative abundances of Euryarchaeota, Patescibacteria, and Synergistota were significantly enriched in rabbits fed with high dosages (600–1000 mg/kg) of EGCG. Conclusively, the addition of large doses of EGCG (400–800 mg/kg) can effectively suppress oxidative stress and alleviate weaning stress, thereby contributing to the protection of post-weaning rabbits.

Abstract Electromyography (EMG) signal is the electrical potential generated by contracting muscle cells. Long-term and accurate EMG monitoring is desirable for neuromuscular function assessment in clinical and the human–computer interfaces. Herein, we report a skin-integrated, biocompatible, and stretchable silicon microneedle electrode (SSME) inspired by the plant thorns. The silicon microneedles are half encapsulated by the polyimide (PI) to enhance the adaptability to deformation and resistance to fatigue. Thorn-like SSME is realized by the semi-additive method with a stretchability of not less than 36%. The biocompatibility of SSME has been verified using cytotoxicity tests. EMG monitoring in motion and long-term has been conducted to demonstrate the feasibility and performance of the SSME, which is compared with a commercial wet electrode. Hopefully, the strategies reported here can lead to accurate and long-term EMG monitoring, facilitating an effective and reliable human–computer interface.

Abstract Implanted bioelectronic devices can form distributed networks capable of sensing health conditions and delivering therapy throughout the body. Current clinically-used approaches for wireless communication, however, do not support direct networking between implants because of signal losses from absorption and reflection by the body. As a result, existing examples of such networks rely on an external relay device that needs to be periodically recharged and constitutes a single point of failure. Here, we demonstrate direct implant-to-implant wireless networking at the scale of the human body using metamaterial textiles. The textiles facilitate non-radiative propagation of radio-frequency signals along the surface of the body, passively amplifying the received signal strength by more than three orders of magnitude (>30 dB) compared to without the textile. Using a porcine model, we demonstrate closed-loop control of the heart rate by wirelessly networking a loop recorder and a vagus nerve stimulator at more than 40 cm distance. Our work establishes a wireless technology to directly network body-integrated devices for precise and adaptive bioelectronic therapies.

In Bacillus thuringenesis (Bt) transgenic cotton, the cotton boll has the lowest insecticidal protein content when compared to the other organs. The present study investigated the effects of amino acid spray application at the peak flowering stage on the cotton boll Bt toxin concentration and yield formation. Boll protein synthesis and carbohydrate conversion were also studied to reveal the fundamental mechanism. Three treatments (i.e., CK, the untreated control; LA1, five amino acids; LA2, 21 amino acids) were applied to two Bt cultivars of G. hirsutum (i.e., the hybrid Sikang 3 and the conventional Sikang 1) in the cotton-growing seasons during 2017 and 2018. Amino acid spray application at the peak flowering stage resulted in an increase of 5.2–16.4% in the boll Bt protein concentration and an increase of 5.5–11.3% in the seed cotton yield, but there was no difference between the two amino acid treatments. In addition, amino acid applications led to increases in the amino acid content, soluble protein content, glutamate pyruvate transaminase (GPT) activity, glutamate oxaloacetate transaminase (GOT) activity, glucose content, fructose content and soluble acid invertase (SAI) activity. This study also found that Bt protein content, enhanced boll number and the weight of opened bolls were closely related to carbon and nitrogen metabolism. The Bt protein content had significant linear positive correlations with amino acid and soluble protein contents. Enhanced boll number had significant linear positive correlations with the GPT and GOT activities from 15–25 days after flowering (DAF). The weight of opened bolls from 55–65 DAF had a significant linear positive correlation with the SAI activity. These results indicate that the enhancement of boll protein synthesis and carbohydrate conversion by amino acid application resulted in a simultaneous increase in the boll Bt protein concentration and cotton lint yield.

Abstract The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

One of the primary threats to coal mine safety production is the sudden extensive fracturing and collapse of thick and hard roof strata. A range of uniaxial compression experiments with acoustic emission (AE) monitoring was performed for studying the mechanical properties and crack evolution of thick and hard roof sandstone specimens. AE temporal response analysis revealed that the damage process of thick and hard roof sandstone specimens exhibited distinct stages. Additionally, AE event localization indicated that microcracks within the thick and hard roof sandstone specimens propagated from the ends to the middle of the specimens during the loading process, eventually leading to severe failure. The b-value analysis demonstrated that during the early loading stage, the scale of internal microcracks within the thick and hard roof sandstone specimens gradually decreased with the optimization of the load-bearing structure. In the later loading stage, the scale of microcracks increased with the deterioration of the load-bearing structure. Furthermore, RA–AF analysis revealed that the specimens experienced combined tensile–shear failure, primarily dominated by tensile failure throughout. The AE characteristics observed during the deformation of thick and hard sandstone can provide references for the monitoring of roof stability and early warning of potential disasters in thick and hard sandstone conditions.

During the establishment of the coal mine goaf reservoir, the strength of the coal pillar dam was weakened by various water–rock interactions triggered by water movement. To explore the influence of the water-bearing state on the shear characteristics of coal pillar dams, the 2–2 coal seam of Shangwan Coal Mine in the Shendong Mining area was taken as the research object and was prepared to coal samples with different moisture contents and different drying-saturation cycles, and the variable angle shear test of coal samples was carried out. The law of water absorption of coal samples under natural and pressurized conditions is obtained. The research results show that the shear characteristics of coal samples change significantly under the action of water, with the increase of moisture content and drying-saturation cycles, the lower the shear strength of coal samples is, the larger the peak shear strain is, and the cohesion and internal friction angle of coal samples decrease linearly. According to the relationship between cohesion, internal friction angle, moisture content, and drying-saturation cycle times, the Mohr–Coulomb model of coal samples considering moisture content and immersion times is established, which contributes to the load-bearing capacity estimation of water-bearing coal mass. Additionally, scanning electron microscope analysis revealed significant changes in the microstructure of coal samples under different moisture states: as the moisture content and dry-saturation cycles increase, the microstructure of the coal samples gradually transforms from orderly and compact to disordered and murky, elucidating the mechanism by which moisture weakens the mechanical properties of the coal samples. The research results provide a useful reference for engineering problems related to the stability evaluation of coal bodies involving the repeated erosion effect of water.

For understanding the mechanical performance and strain energy evolution mechanism of thick hard roof sandstone samples, a sequence of uniaxial compression trials with acoustic emission (AE) monitoring were carried out. The results indicate: (1) The stress-strain curve of the thick hard roof sandstone specimens exhibits distinct stage characteristics. Based on the evolvement of instantaneous axial stiffness, it is separated into Fracture Closure Phase, Elastic Deformation Phase, Steady Fracture Expansion Phase, Unsteady Fracture Expansion Phase, and Post-Peak Phase. (2) The AE energy and cumulative count curves of the thick hard roof sandstone specimens also exhibit significant stage characteristics and can be mutually corroborated with the stage division of the stress-strain curve. (3) Based on the energy conservation principle, the evolution of strain energy density in the thick hard roof sandstone specimens under uniaxial compression loading was analyzed, and plastic strain energy increment was employed to study the stage characteristics of strain energy dissipation. (4) A damage constitutive model for the thick hard roof sandstone specimens was constructed, considering the characteristics of strain energy dissipation. This model effectively describes the stress-strain relationship among the samples, which undergo strain hardening, strain softening, and sudden destruction.

To summarize current prevalence and drug resistance rate of Escherichia coli (E. coli) among orthopaedic surgical site infections (SSIs) in China from English and Chinese language sources. Online databases were searched to collect related researches. A meta-analysis was performed to analyse prevalence and 95 % confidence interval (CI) of E. coli among patients with orthopedic surgical site infections. Meta-regression analysis was used to investigate the difference in the prevalence and antimicrobial resistance of E. coli among different subgroups. A total of 52 studies were enrolled into our meta-analysis, with a total of 31,285 strains isolated. The overall E. coli prevalence was 13.4 % (95 % CI 11.6–15.5). Study design (R2 = 8.98) and sample size (R2 = 10.95) might be potential sources of heterogeneity and there were no significant differences in risk of bias (R2 = 0.28), study time (R2

Abstract Background Combinations of drugs are becoming increasingly common in oncology treatment. In some cases, patients can benefit from the interaction between two drugs, although there is usually a higher risk of developing toxicity. Due to drug–drug interactions, multidrug combinations often exhibit different toxicity profiles than those of single drugs, leading to a complex trial scenario. Numerous methods have been proposed for the design of phase I drug combination trials. For example, the two-dimensional Bayesian optimal interval design for combination drug (BOINcomb) is simple to implement and has desirable performance. However, in scenarios where the lowest and starting dose is close to being toxic, the BOINcomb design may tend to allocate more patients to overly toxic doses, and select an overly toxic dose combination as the maximum tolerated dose combination. Method To improve the performance of BOINcomb in the above extreme scenarios, we widen the range of variation of the boundaries by setting the self-shrinking dose escalation and de-escalation boundaries. We refer to the new design as adaptive shrinking Bayesian optimal interval design for combination drug (asBOINcomb). We conduct a simulation study to evaluate the performance of the proposed design using a real clinical trial example. Results Our simulation results show that asBOINcomb is more accurate and stable than BOINcomb, especially in some extreme scenarios. Specifically, in all ten scenarios, the percentage of correct selection is higher than the BOINcomb design within 30 to 60 patients. Conclusion The proposed asBOINcomb design is transparent and simple to implement and can reduce the trial sample size while maintaining accuracy compared with the BOINcomb design.

A systematic analysis of the spatiotemporal evolution patterns and factors influencing ecological land (EL) can support the optimization of EL protection policies and ensure the stability of regional ecosystems. Based on remote sensing data, using the gravity center shift model, the landscape pattern index, and the equivalent factor method, the characteristics of EL evolution in the Beijing–Tianjin–Hebei (BTH) region from 1980 to 2020 were analyzed. A fixed-effects model was used to quantitatively explore the factors influencing EL evolution and heterogeneity analysis. The results are as follows: (1) The EL area exhibited a trend of initial decrease followed by a subsequent increase during the study period. The most significant area transfer occurred between cropland and EL, but, after the 21st century, the proportion of area transfer between construction land and EL noticeably increased. (2) The compactness and fragmentation of EL showed a certain spatiotemporal stability, but the spatial distribution of compactness and fragmentation hot and cold spots exhibited significant differences. The fragmentation hot spots mainly displayed a strip distribution, while those of compactness showed a clustered distribution. (3) Although the ecosystem service value in the BTH region demonstrated dynamic “M”-shaped changes, the distribution of hot and cold spots still exhibited spatial stability. Regulating services consistently occupied a higher proportion of the sub-service functions, while cultural services still needed further enhancement. (4) Factors influencing the evolution of areas and values demonstrated similarities. The landscape was significantly influenced by construction land, showing a non-linear “U”-shaped relationship with fragmentation. Different economic development gradients and altitudes exhibited differentiated characteristics in terms of their influencing factors. This study provides scientific support for dynamically and precisely adjusting governmental EL management policies, contributing to the sustainable development of regional socio-economics.

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.

The utilization of Erythritol/xylitol eutectic material for low-temperature thermal energy storage and thermal management holds great promise. However, its inability to undergo spontaneous nucleation and crystallization poses a significant obstacle. This research paper introduces a novel nucleation technique that combines gas injection agitation and seeding to address this issue. The study aims to investigate the impact of gas injection tube diameter, thermal environment, and gas injection duration on the nucleation and crystallization characteristics of the material. Experimental analysis reveals that, under optimal conditions, the solidification enthalpy reaches 203.1 J/g, equivalent to 85% of the melting enthalpy. Additionally, the material exhibits excellent thermal cycle stability, with no observed phase separation or deterioration after 100 heating and cooling cycles. Furthermore, the influence of Multi-Walled Carbon Nanotube (MWCNT) nanoparticle additives on nucleation is explored. Different MWCNT additive mass fractions are compared. The obtained results underscore the significance of understanding the effects of gas injection parameters and nanoparticle additives on nucleation and crystallization processes. The enhanced solidification enthalpy, remarkable thermal cycle stability, and insights into MWCNT effects pave the way for broader applications of this promising phase change material in thermal energy storage and thermal management.

With the capability of interconversion between electrical and mechanical energy, piezoelectric materials have been revolutionized by the implementation of perovskite-piezoelectric-ceramic-based studies over 70 years. In particular, the market of piezoelectric ceramics has been dominated by lead zirconate titanate for decades. Nowadays, the research on piezoelectric ceramics is largely driven by cutting-edge technological demand as well as the consideration of a sustainable society. Hence, environmental-friendly lead-free piezoelectric materials have emerged to replace lead-based Pb(Zr,Ti)O3 (PZT) compositions. Owing to the inherent high mechanical quality factor (Qm) and low energy loss, (Li,Na)NbO3 (LNN) materials have recently drawn increasing attention and brought advantages to high-power piezoelectric applications. Although the crystallographic structures of LNN materials were intensively investigated for decades, the technical strategies for electrical performance are still limited. As a result, the property enhancement appears to have approached a plateau. This review traces the progress in the development of LNN materials, starting from the polymorphism in terms of the crystal structures, phase transitions, and local structural distortions. Then, the key milestone works on the functional tunability of LNN are reviewed with emphasis on involved engineering approaches. The exceptional performance at a large vibration velocity makes LNN ceramics promising for high-power applications, such as ultrasonic welding (UW) and ultrasonic osteotomes (UOs). The remaining challenges and some strategic insights for synergistically engineering the functional performance of LNN piezoceramics are also suggested.

Multilayers comprising alternating soft and hard layers offer enhanced toughness compared to all-hard structures. Here authors reveal how the hard and soft components in Ruddlesden–Popper perovskites work cooperatively to resist deformation under pressure, informing the design of alternating superlattices for engineering applications.

Abstract The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881–5.966; P

This study effectively synthesized N,N'-(diazene-1,2-diylbis(5-amino-[1,2,4]triazolo[1,5-a][1,3,5]triazine-2,7-diyl)) dinitramide (3) by using 3,5-diamino-1,2,4-triazole as a starting material combining hydrogen bonds (HBs) and strong π-π stacking interaction between layers. Moreover, two fused rings were linked by an azo group to expand the conjugated compound, resulting in a shorter interlayer distance. The new compound and its energetic salts (4–6) were fully characterized through elemental analysis, IR spectroscopy, 1H and 13C NMR spectroscopy, and thermal analysis. The heats of formation and detonation properties of these compounds were calculated using Gaussian 09 and EXPLO5, respectively. The calculated results show that compounds 3–6 have both low impact and friction sensitivities (IS ​> ​40 ​J; FS ​> ​360 ​N) and favorable densities and detonation properties (ρ: 1.81–1.96 ​g·cm−3; vD: 7965–8248 ​m·s−1; p: 24.9–31.4 ​GPa). Therefore, they are promising candidates for high-energy and insensitive explosives.

Objective: As a high computation cost discipline, nuclear science and engineering still relies heavily on traditional high performance computing (HPC) clusters. However, the usage of traditional HPC for nuclear science and engineering has been limited due to the poor flexibility, the software compatibility and the poor user interfaces. Virtualized/virtual HPC (vHPC) can mimic an HPC by using a cloud computing platform. In this work, we designed and developed a vHPC system for employment in nuclear engineering. Methods: The system is tested using the computation of the number π by Monte Carlo and an X-ray digital imaging system simulation. The performance of the vHPC system is compared with that of the traditional HPCs. Results: As the number of the simulated particles increases, the virtual cluster computing time grows proportionally. The time used for the simulation of the X-ray imaging was about 21.1 ​h over a 12 kernels virtual server. Experimental results show that the performance of virtual cluster computing and the actual physical machine is almost the same. Conclusions: From these tests, it is concluded that vHPC is a good alternative for employing in nuclear engineering. The proposed vHPC in this paper will make HPC flexible and easy to deploy.

Abstract Chronic diseases are currently posing a major challenge not only to our life expectancy and healthspan but also to the healthcare system, as patients will need continual monitoring, treatment, and care to mitigate some of the severe health complications that may arise. Merely frequent visits to medical facilities and clinics may not be sufficient. Home‐based point‐of‐care diagnosis and monitoring may be needed for the prevention and/or management of long‐term complications. Recent advances in materials, fabrication methods, and bioelectronics have led to some epidermal systems that can measure critical physiological parameters and provide long‐term monitoring of several chronic diseases. In this review, it is systematically outlined the progress of epidermal bioelectronics aimed at managing common chronic diseases, such as cardiovascular diseases, diabetes, and chronic wounds. Flexible and stretchable materials with related engineering approaches that render wearability are also discussed. Finally, a list of current challenges, future perspectives as well as potential research directions with the aim towards better translation in bringing these wearable technologies from the laboratory to the clinic and market are presented.

Transition metal dichalcogenides (TMDs) and perovskites are among the most attractive and widely investigated semiconductors in the recent decade. They are promising materials for various applications, such as photodetection, solar energy harvesting, light emission, and many others. Combining these materials to form heterostructures can enrich the already fascinating properties and bring up new phenomena and opportunities. Work in this field is growing rapidly in both fundamental studies and device applications. Here, we review the recent findings in the perovskite-TMD heterostructures and give our perspectives on the future development of this promising field. The fundamental properties of the perovskites, TMDs, and their heterostructures are discussed first, followed by a summary of the synthesis methods of the perovskites and TMDs and the approaches to obtain high-quality interfaces. Particular attention is paid to the TMD-perovskite heterostructures that have been applied in solar cells and photodetectors with notable performance improvement. Finally through our analysis, we propose an outline on further fundamental studies and the promising applications of perovskite-TMD heterostructures.

Hematopoietic stem cells (HSCs) are important for the hematopoietic system because they can self-renew to increase their number and differentiate into all the blood cells. At a steady state, most of the HSCs remain in quiescence to preserve their capacities and protect themselves from damage and exhaustive stress. However, when there are some emergencies, HSCs are activated to start their self-renewal and differentiation. The mTOR signaling pathway has been shown as an important signaling pathway that can regulate the differentiation, self-renewal, and quiescence of HSCs, and many types of molecules can regulate HSCs’ these three potentials by influencing the mTOR signaling pathway. Here we review how mTOR signaling pathway regulates HSCs three potentials, and introduce some molecules that can work as the regulator of HSCs’ these potentials through the mTOR signaling. Finally, we outline the clinical significance of studying the regulation of HSCs three potentials through the mTOR signaling pathway and make some predictions.

Due to its widespread occurrence and high mortality rate, hepatocellular carcinoma (HCC) is an abhorrent kind of cancer. Immunotherapy is a hot spot in the field of cancer treatment, represented by immune checkpoint inhibitors (ICIs), which aim to improve the immune system’s ability to recognize, target and eliminate cancer cells. The composition of the HCC immune microenvironment is the result of the interaction of immunosuppressive cells, immune effector cells, cytokine environment, and tumor cell intrinsic signaling pathway, and immunotherapy with strong anti-tumor immunity has received more and more research attention due to the limited responsiveness of HCC to ICI monotherapy. There is evidence of an organic combination of radiotherapy, chemotherapy, anti-angiogenic agents and ICI catering to the unmet medical needs of HCC. Moreover, immunotherapies such as adoptive cellular therapy (ACT), cancer vaccines and cytokines also show encouraging efficacy. It can significantly improve the ability of the immune system to eradicate tumor cells. This article reviews the role of immunotherapy in HCC, hoping to improve the effect of immunotherapy and develop personalized treatment regimens.

Electronic textiles should maintain performance against repeated mechanical, thermal and chemical stresses during daily activities. Here, authors demonstrate digital embroidery of robust liquid metal-based fibres with wireless functionalities.

Hydrogen from biomass, as a promising alternative fuel, is becoming considerably attractive due to its high energy density and clean emissions. The aqueous phase reforming (APR) of biomass-derived oxygenated hydrocarbons and water is a renewable and efficient pathway for hydrogen production and shows great potential. However, the key to the application of this technique is to develop catalysts with high hydrogen productivity. In this work, we first synthesized polyaniline–platinum (PANI-Pt) organo-metallic hybrid precursors and then obtained a high-loaded (~32 wt.% Pt) and highly dispersed (~3 nm Pt particles) Pt@NC−400 catalyst after pyrolysis at 400 °C, and the nanoparticles were embedded in a nitrogen-doped carbon (NC) support. The Pt@NC−400 catalyst showed an almost three times higher hydrogen production rate (1013.4 μmolH2/gcat./s) than the commercial 20% Pt/C catalyst (357.3 μmolH2/gcat./s) for catalyzing methanol–water reforming at 210 °C. The hydrogen production rate of 1,2-propanediol APR even reached 1766.5 μmolH2/gcat./s over the Pt@NC−400 catalyst at 210 °C. In addition, Pt@NC−400 also exhibited better hydrothermal stability than 20% Pt/C. A series of characterizations, including ICP, XRD, TEM, SEM, XPS, N2 physisorption, and CO chemisorption, were conducted to explore the physiochemical properties of these catalysts and found that Pt@NC−400, although with higher loading than 20% Pt/C (~23 wt.% Pt, ~4.5 nm Pt particle), possessed a smaller particle size, a more uniform particle distribution, a better pore structure, and more Pt metal active sites. This study provides a strategy for preparing high-loaded and highly dispersed nanoparticle catalysts with high hydrogen productivity and sheds light on the design of stable and efficient APR catalysts.

A passive responsive smart window is an emerging energy-saving building facility that does not require an active energy supply due to its passive excitation characteristics, which can fundamentally reduce energy consumption. Therefore, achieving passive excitation is the key to the application of such smart windows. In this paper, VO2 is used as a critical raw material for the preparation of smart windows, and we researched the feasibility of its phase transition function and hydrophobic self-cleaning function. VO2 has the characteristic of undergoing a reversible phase transition between metal and insulator under certain temperature conditions and can selectively absorb spectrum at different wavelengths while still maintaining a certain visible light transmission rate, making it a reliable material for smart window applications. The one-step hydrothermal method was used in this work, and different concentrations of tungsten (W) elements were utilized for doping to reduce the VO2 phase transition temperature to 35 °C and even below, thus adapting to the ambient outdoor temperature of the building and enabling the smart window to achieve a combined solar modulation capability of 14.5%. To ensure the environmental adaptability and anti-fouling self-cleaning function of the smart window, as well as to extend the usage period of the smart window, we have modified the smart window material to be hydrophobic, resulting in an environmental surface contact angle of 152.93°, which is a significant hydrophobic improvement over the hydrophilic properties of inorganic glass itself. The realization of the ideal phase transition function and the self-cleaning function echoes the social trend of environmental protection, enriches the use of scenarios and achieves energy saving and emission reduction.

To provide further insight into humid air condensation on hybrid surfaces, an experiment was conducted to visually investigate the condensation process on wettability-interval grooved surfaces, which had hydrophobic ridges and hydrophilic grooves. The droplet dynamic behavior and heat transfer performance of condensation on a wettability-interval grooved surface were explored and compared with four other functional surfaces, including the plain hydrophilic surface, plain hydrophobic surface, hydrophilic grooved surface, and hydrophobic grooved surface. The presence of hydrophobic ridges perpendicular to the groove direction and hydrophilic grooves allowed for the exclusion and easy spreading of droplets, respectively. Compared with the other four functional surfaces, the coupling phenomena during condensation, i.e., the spontaneous suction and directional drainage via hydrophilic grooves, were only found on the wettability-interval grooved surface. These could not only remove condensate quickly but also suppress the formation of the flooded liquid film, which was beneficial to the enhancement of heat transfer performance. It was proven by the experimental results that at subcooling 12 K, the condensation heat flux on the wettability-interval grooved surface reached 1280 W/m2, which was 1.25 times that of the plain hydrophobic surface (1030 W/m2), and 15% higher than that of the hydrophobic grooved surface (1110 W/m2). This indicated that the wettability-interval microgrooves could effectively enhance humid air condensation heat transfer performance.

Abstract Background The rhizosphere is the narrow zone of soil immediately surrounding the root, and it is a critical hotspot of microbial activity, strongly influencing the physiology and development of plants. For analyzing the relationship between the microbiome and metabolome in the rhizosphere of tea (Camellia sinensis) plants, the bacterial composition and its correlation to soil metabolites were investigated under three different fertilization treatments (unfertilized, urea, cow manure) in different growing seasons (spring, early and late summer). Results The bacterial phyla Proteobacteria, Bacteroidetes, Acidobacteria and Actinobacteria dominated the rhizosphere of tea plants regardless of the sampling time. These indicated that the compositional shift was associated with different fertilizer/manure treatments as well as the sampling time. However, the relative abundance of these enriched bacteria varied under the three different fertilizer regimes. Most of the enriched metabolic pathways stimulated by different fertilizer application were all related to sugars, amino acids fatty acids and alkaloids metabolism. Organic acids and fatty acids were potential metabolites mediating the plant-bacteria interaction in the rhizosphere. Bacteria in the genera Proteiniphilum, Fermentimonas and Pseudomonas in spring, Saccharimonadales and Gaiellales in early summer, Acidobacteriales and Gaiellales in late summer regulated relative contents of organic and fatty acids. Conclusion This study documents the profound changes to the rhizosphere microbiome and bacterially derived metabolites under different fertilizer regimes and provides a conceptual framework towards improving the performance of tea plantations.

The complex processes of action of Chinese medicines and their formulations can be studied in terms of complex heterogeneous networks, however multiple diseases are different from one disease. In this study, we proposed a graph neural network-based modelling strategy to explore the material basis and mechanisms of the formulae under multiple disease conditions, exemplified by Xuefu Zhuyu Decoction for stable angina pectoris and unstable angina pectoris. Our modelling approach consists of two parts, a feature part and a model part. In the feature part, we calculated four similarities and their combinations in the similarity network as features of nodes of the heterogeneous network, using a variety of algorithms. In the model part, both the multi-label classification model for compounds and the link prediction model for compounds-targets were performed in six model comparison experiments and four partial ablation experiments. We confirmed that the GraphSAGE-based model was the best performing multi-label classification model while the GAT-based model was the best performing link prediction model, and that the full model with various similarity contents was optimal. Good generalization ability of the model was demonstrated through generalization ability experiments. In the case study, the model was used to predict potential compound-target interactions for marker targets and the reliability of the predictions was demonstrated by molecular docking and literature mining. In conclusion, the model successfully predicted the known material basis and mechanisms and also predicted unknown compound-marker target interactions. The proposed modelling approach can be extended to the study of other formulations.

Abstract Transition metal chalcogenides are attractive electrocatalysts for oxygen evolution reaction (OER) or hydrogen evolution reaction (HER) due to their natural abundance and diverse structure. Herein, nickel sulfides (Ni3S2) and nickel/cobalt sulfides nanohybrid have been in situ fabricated on nickel foam (NF) by a facile hydrothermal method with sodium sulfide (Ss), L‐cysteine (Lc) or thiourea (Tu) as a sulfur source, respectively. The results show that sulfur source has a great influence on the phase structure, morphology and electrocatalytic performance of transition metal sulfides. The nickel sulfide with the sodium sulfide as a sulfur source (NiSs) shows better HER and OER activity in 1 M KOH. With the Co‐doping, three‐dimensional honeycomb‐like NiCoSs nanosheet clusters exhibits the enhanced electrocatalysis properties with overpotentials of only 168 mV at 10 mA cm–2 for HER and 234 mV at 20 mA cm–2 for OER, respectively. The NiCoSs shows the good bifunctional activities for overall water splitting and presents considerable stability for 24 hours. The good electrochemical activities of metal sulfides by using inorganic sodium sulfide can be attributed to the large exposed surface area and heterostructure compositions of Co9S8 and Ni3S2.