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This study investigates the evolutions of microstructure and performance of TiNbZrTaHf-based alloys from equiatomic high-entropy alloys to Ti-rich dilute alloys. A novel biocompatible alloy, Ti50Nb12.5Zr12.5Ta12.5Hf12.5, was developed with a high yield strength of 839 ± 12 MPa, low modulus of 61.5 GPa, low magnetic susceptibility of ∼1.99 × 10−6 cm3g−1, and unprecedented tensile plasticity of 28.7 ± 2.2%. The study discusses the underlying mechanisms responsible for these superior performances, attributing the exceptional plasticity to the activation of cross-slip dislocations, enhanced dynamic recovery and high resistance to crack propagation. The findings provide new insights into the development of biomedical titanium alloys. This study introduces a novel biocompatible concentrated alloy with high strength, low modulus and unprecedented ductility, providing new insights for developing high-performance biomedical titanium alloys.

The importance of prompt diagnosis and early stenting of an aortic rupture cannot be overemphasized. We present a case of thoracic aortic rupture in a middle-aged gentleman who had recently suffered coronavirus disease 2019. The case was further complicated by the development of an unexpected spinal epidural hematoma.

Here we summarize the most recent findings in the chemical-, photo-, or enzyme-triggered generation of nitrogen and oxygen anions leading to the formation of quinone methide intermediates (QMIs). This short review is divided into two categories: generation of nitrogen and oxygen anions. Based on quinone methide intermediates (QMIs), proximate capture of a wide range of proteins has been widely determined and studied. Generally, the triggers include, photoirradiation using 365/254 nm UV light, small molecules (ROS/TBAF/s-tetrazine), metal catalysis (iridium catalysis), and enzymes (NQO1/β-galactosidase). New directions including far-red light, heat, force, microwave, and more practical approaches are explored and illustrated.1 Introduction2 Generation of the Nitrogen Anion3 Generation of the Oxygen Anion4 Conclusion

Hysterectomy is one of the most common gynecological surgeries conducted around the world. Previous studies reported inconsistent results on depressive symptoms experienced after hysterectomy. This study explored the association between hysterectomy with or without oophorectomy and the use of antidepressants.This cross-sectional study included 4888 subjects between 20 and 80 years old who participated in the US National Health and Nutrition Examination Survey (NHANES) between 2015 and 2018. The associations between hysterectomy with or without oophorectomy and the use of antidepressants were estimated using multivariable logistic regression models.There was a positive relationship between hysterectomy, both with and without oophorectomy, and the use of antidepressants after adjusting for all potential confounders (OR = 2.13, 95 % CI = 1.43-3.17, p = 0.000; OR = 2.04, 95 % CI = 1.35-3.06 p = 0.001). In the subgroup analysis stratified by race, a positive association between hysterectomy without oophorectomy was found among non-Hispanic white women (OR = 1.89, 95 % CI = 1.04-3.44, p = 0.038) and women of other races (OR = 3.14, 95 % CI = 1.30-7.56, p = 0.010), and a positive association between hysterectomy with oophorectomy was found among non-Hispanic black women (OR = 3.09, 95 % CI = 1.15-8.27, p = 0.024). However, no association was found among non-Hispanic black and Mexican American women who had undergone hysterectomy with oophorectomy, and it was not reported in women of non-Hispanic white, Mexican American or other race who underwent hysterectomy with oophorectomy.This study suggested that hysterectomy was significantly associated with antidepressant use, but the extent of the associations may vary by race.

To measure the extended-range neutron spectra and calibrate the extended-range neutron dosemeters of the China initiative Accelerator-Driven System (CiADS), an Extended-range Bonner Sphere Spectrometer (EBSS) has been developed. The EBSS was designed based on the PHITS codes, investigating various combinations of materials and diameters of the neutron moderators and the neutron multipliers for extended-range neutrons. Finally, seven polyethylene-only spheres and seven extended-range spheres were selected and subsequently built. The neutron multipliers of the extended-range spheres embedded concentric shells of lead, copper and tungsten. The response functions of the EBSS were analyzed and experimentally validated. It was subsequently tested with 252Cf neutron source and cosmic ray neutron source. The results demonstrate that the EBSS is capable of accurately measuring neutron spectra.

Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.

ConspectusThe development of palladium-catalyzed cross-coupling methods for the activation of C(sp

Immune subtyping is an important way to reveal immune heterogeneity, which may contribute to the diversity of the progression and treatment in head and neck squamous cell carcinoma (HNSCC). However, reported immune subtypes mainly focus on levels of immune infiltration and are mostly based on a mono-omics profile. This study aimed to identify a comprehensive immune subtype for HNSCC via multi-omics clustering and build a novel subtype prediction system for clinical application. Data were obtained from The Cancer Genome Atlas database and our independent multicenter cohort. Multi-omics clustering was performed to identify 3 clusters of 499 patients in The Cancer Genome Atlas based on immune-related gene expression and somatic mutations. The immune characteristics and biological features of the obtained clusters were revealed by bioinformatics, and 3 immune subtypes were identified: 1) adaptive immune activation subtype predominantly enriched in T cells, 2) innate immune activation subtype predominantly enriched in macrophages, and 3) immune desert subtype. Subsequently, the clinical implications of each subtype were analyzed per clinical epidemiology. We found that adaptive immune activation showed better survival outcomes and had a similar response to chemotherapy with innate immune activation, whereas immune desert might be relatively resistant to chemotherapy. Moreover, a subtype prediction system was developed by deep learning with whole slide images and named HISMD: HNSCC Immune Subtypes via Multi-omics and Deep Learning. We endowed HISMD with interpretability through image-based key feature extraction. The clinical implications, biological significances, and predictive stability of HISMD were successfully verified by using our independent multicenter cohort data set. In summary, this study revealed the immune heterogeneity of HNSCC and obtained a novel, highly accurate, and interpretable immune subtyping prediction system. For clinical implementation in the future, additional validation and utility studies are warranted.

Leaf stoichiometry can characterize plant ecological strategies and correlate with plant responses to climate change. The role of vascular epiphytes in the ecosystem processes of tropical and subtropical forest ecosystems cannot be ignored. Vascular epiphytes are very vulnerable to climate change, however, the relationship between the response of epiphytes to climate change and leaf stoichiometry is not well understood. We present data for 19 vascular epiphyte species that were collected during four consecutive censuses (in 2005, 2010, 2015, and 2020) over 15 years in a subtropical montane cloud forest. We assessed the relationships between the population dynamics and leaf stoichiometry of these vascular epiphytes. Experiencing an extreme drought, 14 of the 19 epiphyte species showed an obvious decrease in the number of individuals, and all species showed negative growth in the number of populations. Subsequently, the total number of individuals gradually recovered, increasing from 7,195 in 2010 to 10,121 in 2015, then to 13,667 in 2020. The increase in the number of vascular epiphyte individuals from 2010 to 2015 was significantly negatively correlated with leaf nitrogen and phosphorus concentration, and was significantly positively correlated with the leaf carbon-nitrogen ratio. Vascular epiphyte populations with higher leaf nutrient concentrations exhibited weaker resilience to the extreme drought, which demonstrated that a resource-conservative strategy was advantageous for the recovery of epiphyte populations. Our findings suggest that ecological stoichiometry can be a useful framework for forecasting the dynamics of vascular epiphyte populations in response to climate change.

Have you ever picked up a stuffed toy and pretended to play with it in your childhood? We are motivated by the novel use of stuffed toys in enhancing extended reality interaction. A key goal of extended reality is to induce the feeling of presence in its users. Naturally mapped control interface has been shown to enhance presence. The literature also indicates that a high degree of freedom tracking is important to extended reality. Based on these observations, we show that a free-form naturally mapped control interface is well-motivated via a theoretical contextualization. We explore the possibility of building such a controller in the form of stuffed toys. To realize stuffed toys as controllers, a novel soft-pose estimator empowered by cage-based deformation is proposed. It is shown to be effective in tracking the poses and deformations of real soft objects even by training with synthetic data only. Three gameplay prototypes are developed to demonstrate that interactive play can be enabled by the soft-pose estimator. They also form the basis for two user studies that validate the success of tracking stuffed toys with the soft-pose estimator for interactive play.

Propofol has been shown to against intestinal reperfusion injury when treated either before or after ischemia, during which mast cell could be activated. The aim of this study was to evaluate the role of propofol in restoring the intestinal epithelial cells integrity disrupted by mast cell activation or the released tryptase after activation in vitro. We investigated the effect of: (1) tryptase on Caco-2 monolayers in the presence of PAR-2 inhibitor or propofol, (2) mast cell degranulation in a Caco-2/LAD-2 co-culture model in the presence of propofol, and (3) propofol on mast cell degranulation. Epithelial integrity was detected using transepithelial resistance (TER) and permeability to fluorescein isothiocyanate (FITC)-dextran (the apparent permeability coefficient, Papp). The expression of junctional proteins zonula occludens-1 (ZO-1/TJP1) and occludin were determined using western blot analysis and immunofluorescence microscopy. The intracellular levels of reactive oxidative species (ROS) and Ca2+ were measured using flow cytometry. Tryptase directly enhanced intestinal barrier permeability as demonstrated by significant reductions in TER, ZO-1, and occludin protein expression and concomitant increases in Papp. The intestinal barrier integrity was restored by PAR-2 inhibitor but not by propofol. Meanwhile, mast cell degranulation resulted in epithelial integrity disruption in the Caco-2/LAD-2 co-culture model, which was dramatically attenuated by propofol. Mast cell degranulation caused significant increases in intracellular ROS and Ca2+ levels, which were blocked by propofol and NAC. Propofol pretreatment can inhibit mast cell activation via ROS/Ca2+ and restore the intestinal barrier integrity induced by mast cell activation, instead of by tryptase.

Cooperative sweep coverage of multiagent systems (MASs) has found broad applications in various fields. This article proposes a scheme to address the sweep coverage problem of MASs within uncertain environments. In the proposed formulation, the coverage region is divided into multiple stripes, of which each has the workload completed by MASs in sequence. When the workload on the current stripe is completed, all the agents switch to the next together. The temporal dependence between the switching time computation and the sweep coverage operation is taken into account, and an online learning strategy is designed to handle environmental uncertainties and balance the workload among agents on the same stripe. Thereby, the distributed sweep coverage algorithm is developed to guarantee the complete sweep coverage, which consists of three operations, i.e., communication, workload partition, and sweeping. Theoretical analysis is afterward conducted to estimate the upper bound for the error between the actual and optimal coverage time. Finally, numerical simulations are carried out to substantiate the effectiveness and superiority of the proposed scheme.

Polymeric aziridines are introduced as a new class of low toxicity two-component crosslinkers for carboxylic resins. Using a combination of industry-standard tests and modern biotechnological approaches, the non-genotoxic nature of these compounds was demonstrated. Mechanical analysis of acrylic films formulated with these polymeric aziridines demonstrated that the high crosslink densities typical for classical aziridine chemistry could be attained. Furthermore, distribution of crosslinker molecules in both wet formulation and dried coating could be controlled by adjusting the stabilizing group of the polymeric aziridine. By tuning this stabilization mechanism, we demonstrated customized functional performance for different coating applications.

Listeria monocytogenes is a typical foodborne pathogen that causes hard-to-treat bacterial infections, mainly due to its ability to form biofilm and enter into a viable but non-culturable state (VBNC). In this study, we investigated the removal effects of four antimicrobial agents on L. monocytogenes biofilms formed at 32°C and 10°C, analysed the resistances of the mature biofilms to antimicrobial agents, and explored the VBNC state of cells in mature biofilms induced by lavender essential oil (LEO). The results showed that the growth of L. monocytogenes was completely inhibited when 1·6% (v/v) of the LEO was added. Meanwhile, the results of the crystal violet staining and XTT reduction method indicated that different concentrations of LEO significantly reduced L. monocytogenes biofilms biomass and metabolic activities, followed by sodium hypochlorite, lactic acid, and hydrogen peroxide. Moreover, the confocal laser scanning microscopy (CLSM) images confirmed that the treated biofilms became thinner, the structure was sparse, and the appearance was blurry. More interestingly, L. monocytogenes biofilms developed at 10°C were less susceptible to the sanitizers than those formed at 32°C. In addition, LEO presented a more significant dispersing effect on the biofilm cells, and 1/2 MIC to 4 MIC of LEO could induce fewer VBNC state cells in biofilm and plankton compared with sodium hypochlorite. This study indicated that the LEO could be considered as an ideal antibiofilm agent for controlling L. monocytogenes. But we should pay attention to the resistance of the biofilms developed at low temperatures.

Bubbles in a liquid rise under gravity and separate to the top. Bubbly liquids exist commonly in nature and play a significant role in energy-conversion, oil and chemical industries. Therefore, understanding how bubbles rise is of great importance. Rheological properties of the fluid have a strong impact on single bubble rise and have been shown to change collective bubble rise at low gas volume fractions significantly. We expect that a viscoelastic fluid can strongly modify the rise of bubbles in more concentrated suspensions. We generate bubbly liquids up to gas fractions of 30 %. We measure the bubble size and the rise velocity in micellar solutions made of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal), a common system to create shear-thinning solutions. We show that when the NaSal concentration is small and the solutions are Newtonian, the bubble rise velocity decreases with increasing volume fraction of bubbles and the relationship between the two follows the Richardson-Zaki prediction. For the shear thinning viscoelastic solutions, the Richardson-Zaki relation no longer applies. Bubble clustering leads to faster rise velocities and a weaker dependence on the bubble volume fraction. At the largest concentration two rise regimes are observed. A fast one similar to that in the other shear thinning samples, followed by a very slow bubble rise. The slow rise velocity is attributed to the smallest bubbles rising so slowly, that at the shear rates around them, the fluid behaves as a Newtonian fluid. Therefore, bubble rise becomes again comparable to Stokes expectations. We also show that the peculiar dependence of the rise velocity with volume fraction of bubbles in the shear thinning viscoelastic solutions can have important implications in flotation as the area flux changes strongly with bubble volume fraction.

Numerical procedure plays a key role in tackling the solutions of nonlinear dynamical systems. With the advent of the age of big data and high-power computing, developing efficient and fast numerical algorithms is an urgent task. This paper extends the Lie derivative discretization algorithm to the nonautonomous nonlinear systems and investigates the numerical solutions of the systems. The periodic solutions of three different classical nonlinear systems are calculated, and the results are compared to those values calculated from the Runge–Kutta fourth-order algorithm, which demonstrated that the Lie derivative algorithm has the advantages of large time step and short computation time.

Aims Apolipoprotein C-II (ApoC-II) is thought to activate lipoprotein lipase (LPL) and is therefore a possible target for treating hypertriglyceridemia. Its relationship with cardiovascular risk has not been investigated in large-scale epidemiologic studies, particularly allowing for apolipoprotein C-III (ApoC-III), an LPL antagonist. Furthermore, the exact mechanism of ApoC-II–mediated LPL activation is unclear. Methods and results ApoC-II was measured in 3141 LURIC participants of which 590 died from cardiovascular diseases during a median (inter-quartile range) follow-up of 9.9 (8.7–10.7) years. Apolipoprotein C-II–mediated activation of the glycosylphosphatidylinositol high-density lipoprotein binding protein 1 (GPIHBP1)–LPL complex was studied using enzymatic activity assays with fluorometric lipase and very low-density lipoprotein (VLDL) substrates. The mean ApoC-II concentration was 4.5 (2.4) mg/dL. The relationship of ApoC-II quintiles with cardiovascular mortality exhibited a trend toward an inverse J-shape, with the highest risk in the first (lowest) quintile and lowest risk in the middle quintile. Compared with the first quintile, all other quintiles were associated with decreased cardiovascular mortality after multivariate adjustments including ApoC-III as a covariate (all P < 0.05). In experiments using fluorometric substrate-based lipase assays, there was a bell-shaped relationship for the effect of ApoC-II on GPIHBP1–LPL activity when exogenous ApoC-II was added. In ApoC-II-containing VLDL substrate-based lipase assays, GPIHBP1–LPL enzymatic activity was almost completely blocked by a neutralizing anti-ApoC-II antibody. Conclusion The present epidemiologic data suggest that increasing low circulating ApoC-II levels may reduce cardiovascular risk. This conclusion is supported by the observation that optimal ApoC-II concentrations are required for maximal GPIHBP1–LPL enzymatic activity.

mRNA FISH of cell state markers

d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.

Analysis of HER2BOW tumors

p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.

HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (WTHER2), exon-16 null (d16HER2), and N-terminally truncated (p95HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion. Tumorigenesis was visualized using whole-gland fluorescent lineage tracing and single-cell molecular pathology. We demonstrate that within weeks of expression, morphologic aberrations were already present and unique to each HER2 isoform. Although WTHER2 cells were abundant throughout the mammary ducts, detectable lesions were exceptionally rare. In contrast, d16HER2 and p95HER2 induced rapid tumor development. d16HER2 incited homogenous and proliferative luminal-like lesions which infrequently progressed to invasive phenotypes whereas p95HER2 lesions were heterogenous and invasive at the smallest detectable stage. Distinct cancer trajectories were observed for d16HER2 and p95HER2 tumors as evidenced by oncogene-dependent changes in epithelial specification and the tumor microenvironment. These data provide direct experimental evidence that intratumor heterogeneity programs begin very early and well in advance of screen or clinically detectable breast cancer.Implications:Although all HER2 breast cancers are treated equally, we show a mechanism by which clinically undetected HER2 isoforms program heterogenous cancer phenotypes through biased epithelial specification and adaptations within the tumor microenvironment.