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The rise of the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae has been increasingly reported in recent years, however, there are few outbreak cases for these producing NDM carbapenemase. In this study, ST65-KL2 and ST11-KL64 hypervirulent and carbapenem-resistant K. pneumoniae (hvCRKP) were identified from two different outbreak cases: (1) clonal spreading of ST65-KL2 in five patients within transplantation wards spanning three months; and (2) clonal transmission of ST11-KL64 in ten patients across 10 months. The representative strains of ST65-KL2 and ST11-KL64 hvCRKP, K22877 and K56649, produced carbapenemase NDM-5 and dual carbapenemases KPC-2 and NDM-13, respectively, and both exhibited high-level carbapenem resistance. Moreover, virulent analysis showed that K22877 and K56649 were hypervirulent and the former possessed stronger virulence. Evolutionary pathways suggested ST65-KL2 and ST11-KL64 hvCRKP could be classified as CR-hvKP (hvKP acquiring carbapenem resistance) and hv-CRKP (CRKP acquiring hypervirulence), respectively. Unexpectedly, ST65-KL2 CR-hvKP showed resistance to ciprofloxacin mediated by plasmid acquisition as its spread, and ST11-KL64 hv-CRKP developed into enhanced virulence and macrophage resistance. Furthermore, compared to the ST65-KL2 CR-hvKP, the ST11-KL64 hv-CRKP tends to cause occult and persistent infection. Global genome analysis revealed ST11-KL64 hv-CRKP and ST65-KL2 CR-hvKP mainly carried blaKPC-2 and had significant differences in Ompk35/36, ybt, resistance and virulence. Effective surveillance should be implemented and novel therapeutic strategies are urgently needed to deal with refractory infections. The hypervirulent and multidrug-resistant K. pneumonia ST65-KL2 CR-hvKP and ST11-KL64 hv-CRKP, pose an intense ability to disseminate and cause high mortality. Resistance and virulence evolution accelerate their threat to human health. [ABSTRACT FROM AUTHOR]

Nanomaterials have been utilized as antibacterial agents due to their distinct mechanism of action, which sets them apart from traditional antibiotics. Cerium oxide nanoparticles (CeO2 NPs) play a crucial role as antibacterial agents because of their minimal toxicity towards healthy cells and their unique antibacterial mechanism, which involves the reversible transition between two valence states of Ce(III)/Ce(IV). In the current study, silica microspheres (SiO2) were applied for the growth of hydroxyapatite (Hap) over the silica surface. Then, the SiO2/hydroxyapatite (SiO2/Hap) nanocomposite was applied for stabilization of the in situ green synthesized cerium oxide nanoparticles (CeO2 NPs) on its surface to assess the antibacterial and cellular viability of orthodontic brackets. The as-prepared SiO2/Hap-CeO2 NPs were fully characterized by different techniques such as FT-IR, XRD, FE-SEM, TEM and ICP-OES analyses. The technique employed to coat the orthodontic bands with SiO2/Hap-CeO2 NPs nanocomposite was the electrostatic spray-assisted vapor deposition method. The antibacterial efficacy of SiO2/Hap-CeO2 NPs nanocomposite against Candida albicans, Streptococcus mutans and Lactobacillus acidophilus was evaluated using the biofilm inhibition test. In the recent study's cellular and molecular component, the treated cells with SiO2/Hap-CeO2 NPs nanocomposite underwent evaluation through MTT assay to determine cytotoxicity on the normal (HUVEC) cell line. In comparison to the control group, the SiO2/Hap-CeO2 NPs nanocomposite group exhibited a 2-log10 decrease in the replication ability of all microorganisms. The group of SiO2/Hap-CeO2 NPs nanocomposite demonstrated a notable decrease in the quantity of C. albicans, S. mutans and L. acidophilus colonies compared to the control group. Application of SiO2/Hap-CeO2 NPs nanocomposite on orthodontic bands resulted in antibacterial properties against oral pathogens. [ABSTRACT FROM AUTHOR]

Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

With the increasingly widespread application of rubber in many fields, there is a growing demand for quantitative characterization of temperature-dependent mechanical properties in high-temperature service environments. The critical tearing energy is an important criterion for determining whether rubber materials will experience tearing instability, while tear strength is a key parameter for rubber materials to resist tearing. It is necessary to quantitatively characterize their evolution with temperature. Current theoretical research mainly relies on fitting a large amount of experimental data, which is not convenient for engineering applications. Therefore, in this work, a temperature-dependent critical tearing energy model is firstly developed based on the force-heat equivalence energy density principle. This model considers the equivalent relationship between the critical tearing energy required for crack instability propagation and the thermal energy stored in the rubber material. It is demonstrated that our model has higher prediction accuracy when compared to other models. Furthermore, combining with the Griffith fracture theory, temperature-dependent tear strength models applicable to three different crack modes are separately established. These models are validated using experimental data for Mode I opening cracks and Mode III tearing cracks, and good consistency is achieved. Additionally, a quantitative analysis of the influence of elastic modulus on tear strength at different temperatures is conducted. This work provides a reliable way for predicting temperature-dependent tearing instability behavior and offers beneficial suggestions for improving the tear strength of rubber materials at different temperatures. [ABSTRACT FROM AUTHOR]

Motile plant tissues can control their configurations and regulate their motion speed according to their specific requirements, which offer various protypes for biomimetic actuators with controlled motion speed. In this perspective, we focus on the speed control of plant tissues and the bioinspired strategies for speed regulation of artificial actuators. We begin with a summary to the strategies and mechanisms of motile plant tissues for controlling motion speed, ranging from ultrafast to ultraslow. We then exemplify the models for fabricating bioinspired artificial actuators and briefly discuss current application scenarios of actuators with varying speeds from ultrafast to ultraslow. Finally, we propose potential strategies for the speed regulation of actuators. [ABSTRACT FROM AUTHOR]

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue–electronics interfaces, however, cannot be standardized, because tissues are soft1–3 and have arbitrary shapes and sizes4–6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10–12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue–electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.Water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex contract by more than 50% of their original length within seconds after wetting and become soft and stretchable hydrogel thin films that can be used in bioelectronic interfaces. [ABSTRACT FROM AUTHOR]

By leveraging their high mobility and small size, insects have been combined with microcontrollers to build up cyborg insects for various practical applications. Unfortunately, all current cyborg insects rely on implanted electrodes to control their movement, which causes irreversible damage to their organs and muscles. Here, we develop a non-invasive method for cyborg insects to address above issues, using a conformal electrode with an in-situ polymerized ion-conducting layer and an electron-conducting layer. The neural and locomotion responses to the electrical inductions verify the efficient communication between insects and controllers by the non-invasive method. The precise "S" line following of the cyborg insect further demonstrates its potential in practical navigation. The conformal non-invasive electrodes keep the intactness of the insects while controlling their motion. With the antennae, important olfactory organs of insects preserved, the cyborg insect, in the future, may be endowed with abilities to detect the surrounding environment. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) architectures have qualitatively expanded the functions of materials and flexible electronics. However, current fabrication techniques for devices constrain their substrates to 2D geometries and current post-shape transformation strategies are limited to heterogenous or responsive materials and are not amenable to free-standing inert plastic films such as polyethylene terephthalate (PET) and polyimide (PI), which are vital substrates for flexible electronics. Here, we realize the shape morphing of homogeneous plastic films for various free-standing 3D frameworks from their 2D precursors by introducing a general strategy based on programming the plastic strain in films under peeling. By modulating the peeling parameters, previously inaccessible free-standing 3D geometries ranging from millimeter to micrometer were predicted theoretically and obtained experimentally. This strategy is applicable to most materials capable of plastic deformation, including polymers, metals, and composite materials, and can even enable 4D transformation with responsive plastic films. Enhanced performance of 3D circuits and piezoelectric systems demonstrates the enormous potential of peeling-induced shape morphing for 3D devices. Shape morphing offers a promising method to transform 2D electronics into 3D structured devices. Here authors show a shape morphing strategy of homogeneous inert plastic thin films into free-standing 3D frameworks by programming the plastic strain in films under peeling. [ABSTRACT FROM AUTHOR]

In order to reduce the drying time and improve the quality of squid in traditional drying methods, a successive two-stage cold air (1 m/s, 22 °C)/hot air (1 m/s, 60 °C)-assisted radio frequency (CA-RF/HA-RF) drying method was developed with a 6 kW, 27.12 MHz RF heating system. Firstly, the drying kinetics and browning kinetics of squid subjected to hot air (HA), HA-RF and CA-RF drying were studied individually. HA-RF (0.86 g/(g·h)) drying resulted in a higher drying rate than solely HA (0.70 g/(g·h)) drying. However, due to the high drying temperature, the browning index of HA-RF drying was 28.23 higher than CA-RF drying. Meanwhile, CA-RF drying caused localized overheating of squid in the falling rate period, resulting in quality damage. Furthermore, a two-stage combined drying method (HA-RF)+(CA-RF) was brought out based on the drying and color changing kinetics. The two-stage combined drying method ensured a medium drying rate (0.77 g/(g·h)) and energy consumption (39.92 ± 2.67 kW·h/kg) while retained better color (Browning index = 35.13), hardness (318.08 ± 3.85 g) and springiness (0.56 ± 0.08). Moisture migration of squid in two-stage drying was investigated using low-field nuclear magnetic resonance method and superior microstructures were obtained by RF combined drying. In summary, the developed (HA-RF)+(CA-RF) successive two-stage drying process retains better color and lower energy consumption. The results provide potential methods to improve the efficiency and quality of aquatic products using combined RF heating technologies. [ABSTRACT FROM AUTHOR]

Background and Objective: Rivaroxaban is a novel oral anticoagulant widely used for thromboprophylaxis in patients with non-valvular atrial fibrillation (NVAF). The present study aimed to develop a population pharmacokinetic (PPK) model for rivaroxaban in Chinese patients with NVAF. Methods: We performed a prospective multicenter study. The plasma concentration of rivaroxaban was directly detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and indirectly by rivaroxaban-calibrated chromogenic anti-Xa assay (STA®). Gene polymorphisms were detected by MassARRAY single nucleotide polymorphism genotyping technology. Nonlinear mixed-effects modeling was used to develop the PPK model for rivaroxaban in patients with NVAF, and we simulated the steady-state rivaroxaban exposures under different dosing strategies in different covariate levels. Results: A total of 150 patients from five centers were recruited, including 263 plasma concentrations detected by HPLC-MS/MS, 2626 gene polymorphisms, and 131 plasma concentrations detected by anti-Xa assay. In our study, an oral one-compartment model was used to describe the pharmacokinetics of rivaroxaban in patients with NVAF. In the final model, the estimated apparent clearance (CL/F) and volume of distribution (V/F) were 5.79 L/h (relative standard error [RSE] 4.4%) and 51.5 L (RSE 5.0%), respectively. Covariates in the final model included creatinine clearance, total bilirubin, rs4728709, and body weight. The simulation results showed that in the 15 mg once-daily dosing regimen, in most instances the maximum plasma concentration at steady state (Cmax,ss) and trough plasma concentration at steady state (Cmin,ss) were in the target range for different covariate levels. When patients were administered rivaroxaban 15 or 20 mg once daily, the Cmax,ss and Cmin,ss in the different bodyweight levels were also in the target range. For patients with the ABCB1 rs4728709 mutation, the Cmin,ss in the 10, 15, and 20 mg once-daily dosing regimens were lower than the target range. The anti-Xa assay was highly linearly correlated with the HPLC-MS/MS method [y = 1.014x − 2.4648 (R2 = 0.97)]. Conclusions: Our study was the first multicenter PPK model for rivaroxaban in Chinese patients with NVAF (Alfalfa-RIVAAF-PPK). The study found that 15 mg once daily may be suitable as the principal rivaroxaban dose for Chinese patients with NVAF. For patients with the rs4728709 mutation, it may be necessary to examine insufficient anticoagulation. We found that the rivaroxaban-calibrated chromogenic anti-Xa assay and HPLC-MS/MS method were highly linearly correlated. Prospective studies with larger sample sizes and real-world studies are needed for further verification. [ABSTRACT FROM AUTHOR]

Optimization of the ratio of electrolyte components is an effective strategy to improve the electrochemical performance of lithium-ion batteries. Herein, a novel method combining sensitivity and simplex method (abbreviated as QY) is proposed for small-scale optimization of the fraction ratio of 1 mol L−1 LiPF6-ethylene carbonate (EC)/diethyl carbonate (DEC) (with the volume ratio of 1: 1). Firstly, the performance indexes (ionic conductivity, charge-transfer impedance, leakage current, and initial coulombic efficiency) that can be obtained within a relatively short time are selected, and then index normalization is performed to analyze the sensitivity of these indexes based on the change of electrolyte composition. Secondly, the leakage current and charge-transfer impedance are recognized as the main index that affect the performance of Li/LiNi0.5Co0.2Mn0.3O2 cells, and the composition is optimized to 1.03 mol L−1 LiPF6-EC/DEC (with the volume ratio of 1.05: 1). Finally, the improved performance of optimized electrolyte is certified, indicating that the method is suitable for optimization of a complex system in a short test period with fewer experiments. [ABSTRACT FROM AUTHOR]

The separation efficiency of photocarriers is an important part of photocatalytic efficiency. Construction of composite with good contact is a hot topic. In this work, Bi2WO6 is successfully connected with BiOI to form the chemical bonding interface through the same crystal unit, where a precipitation transformation phenomenon is revealed. The chemical bonding interface is conducive to transmission and separation of photocarriers to realize rapid and stable transport and separation through the interface, which is based on the photocurrent density of Bi2WO6/BiOI (BWOI) is about 6 and 40 times higher than Bi2WO6 and BiOI, and the transfer resistance of BWOI is around 5 and 10 times lower than Bi2WO6 and BiOI. Thus, the photocatalytic activity of BWOI is 2.8 and 33.35 times as much as those of Bi2WO6 and BiOI. During the photocatalysis process, photogenerated holes (h+) and superoxide radical (·O2−) are the main oxidizers, and the constructed the chemical bonding interface displays excellent photostability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-β (Aβ)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aβ-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid β-protein fragment 25–35 (Aβ25–35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aβ25–35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aβ25–35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aβ25–35-induced injuries. Syringin protected against Aβ25–35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aβ25–35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD. [ABSTRACT FROM AUTHOR]

The lipid droplet (LD) is a highly dynamic organelle that maintains cellular lipid homeostasis in addition to storing energy sources. Current research suggests LDs are responsible for the transportation, storage and lipolysis-driven mobilization of lipids within cells. Here, we review the landscape of evidence for LD involvement in regulating lipid homeostasis. LD interactions with other organelles, particularly the endoplasmic reticulum, mitochondria, lysosomes (or vacuoles in yeast), and peroxisomes, highlight their importance for lipid transfer and metabolism. [ABSTRACT FROM AUTHOR]

Studying the wetting behaviors of multicellular spheroids is crucial in the fields of embryo implantation, cancer propagation, and tissue repair. Existing strategies for controlling the wetting of multicellular spheroids mainly focus on surface chemistry and substrate rigidity. Although topography is another important feature in the biological micro-environment, its effect on multicellular spheroid wetting has seldom been explored. In this study, the influence of topography on the surface wetting of multicellular spheroids was investigated using subcellularpatterned opal films with controllable colloidal particle diameters (from 200 to 1,500 nm). The wetting of hepatoma carcinoma cellular (Hep G2) spheroids was impaired on opal films compared with that on flat substrates, and the wetting rate decreased as colloidal particle diameter increased. The decrement reached 48.5% when the colloidal particle diameter was 1,500 nm. The subcellular-patterned topography in opal films drastically reduced the cellular mobility in precursor films, especially the frontier cells in the leading edge. The frontier cells failed to form mature focal adhesions and stress fibers on micro-patterned opal films. This was due to gaps between colloidal particles leaving adhesion vacancies, causing weak cell-substrate adhesion and consequent retarded migration of Hep G2 spheroids. Our study manifests the inhibiting effects of subcellular-patterned topography on the wetting behaviors of multicellular spheroids, providing new insight into tissue wetting-associated treatments and biomaterial design. [ABSTRACT FROM AUTHOR]