Tunable Chemical Disorder in Concentrated Alloys: Defect Physics and Radiation Performance.

The development of advanced structural alloys with performance meeting the requirements of extreme environments in nuclear reactors has been long pursued. In the long history of alloy development, the search for metallic alloys with improved radiation tolerance or increased structural strength has relied on either incorporating alloying elements at low concentrations to synthesize so-called dilute alloys or incorporating nanoscale features to mitigate defects. In contrast to traditional approaches, recent success in synthesizing multicomponent concentrated solid-solution alloys (CSAs), including medium-entropy and high-entropy alloys, has vastly expanded the compositional space for new alloy discovery. Their wide variety of elemental diversity enables tunable chemical disorder and sets CSAs apart from traditional dilute alloys. The tunable electronic structure critically lowers the effectiveness of energy dissipation via the electronic subsystem. The tunable chemical complexity also modifies the scattering mechanisms in the atomic subsystem that control energy transport through phonons. The level of chemical disorder depends substantively on the specific alloying elements, rather than the number of alloying elements, as the disorder does not monotonically increase with a higher number of alloying elements. To go beyond our knowledge based on conventional alloys and take advantage of property enhancement by tuning chemical disorder, this review highlights synergistic effects involving valence electrons and atomic-level and nanoscale inhomogeneity in CSAs composed of multiple transition metals. Understanding of the energy dissipation pathways, deformation tolerance, and structural stability of CSAs can proceed by exploiting the equilibrium and non-equilibrium defect processes at the electronic and atomic levels, with or without microstructural inhomogeneities at multiple length scales. Knowledge of tunable chemical disorder in CSAs may advance the understanding of the substantial modifications in element-specific alloy properties that effectively mitigate radiation damage and control a material's response in extreme environments, as well as overcome strength-ductility trade-offs and provide overarching design strategies for structural alloys.

Association between single and multiple cardiometabolic diseases and all-cause mortality among Chinese older adults: A prospective, nationwide cohort study.

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

The genome of Eleocharis vivipara elucidates the genetics of C3-C4 photosynthetic plasticity and karyotype evolution in the Cyperaceae.

Eleocharis vivipara, an amphibious sedge in the Cyperaceae family, has several remarkable properties, most notably its alternate use of C3 photosynthesis underwater and C4 photosynthesis on land. However, the absence of genomic data has hindered its utility for evolutionary and genetic research. Here, we present a high-quality genome for E. vivipara, representing the first chromosome-level genome for the Eleocharis genus, with an approximate size of 965.22 Mb mainly distributed across 10 chromosomes. Its Hi-C pattern, chromosome clustering results, and one-to-one genome synteny across two subgroups indicates a tetraploid structure with chromosome count 2n = 4x = 20. Phylogenetic analysis suggests that E. vivipara diverged from Cyperus esculentus approximately 32.96 million years ago (Mya), and underwent a whole-genome duplication (WGD) about 3.5 Mya. Numerous fusion and fission events were identified between the chromosomes of E. vivipara and its close relatives. We demonstrate that E. vivipara has holocentromeres, a chromosomal feature which can maintain the stability of such chromosomal rearrangements. Experimental transplantation and cross-section studies showed its terrestrial culms developed C4 Kranz anatomy with increased number of chloroplasts in the bundle sheath (BS) cells. Gene expression and weighted gene co-expression network analysis (WGCNA) showed overall elevated expression of core genes associated with the C4 pathway, and significant enrichment of genes related to modified culm anatomy and photosynthesis efficiency. We found evidence of mixed nicotinamide adenine dinucleotide - malic enzyme and phosphoenolpyruvate carboxykinase type C4 photosynthesis in E. vivipara, and hypothesize that the evolution of C4 photosynthesis predates the WGD event. The mixed type is dominated by subgenome A and supplemented by subgenome B. Collectively, our findings not only shed light on the evolution of E. vivipara and karyotype within the Cyperaceae family, but also provide valuable insights into the transition between C3 and C4 photosynthesis, offering promising avenues for crop improvement and breeding.

Osmotic-Induced Reconfiguration and Activation in Membranized Coacervate-Based Protocells.

The design and construction of synthetic protocells capable of stimuli response and homeostatic regulation is an important challenge for synthetic protobiology. Here, we develop a step toward the construction of model protocells capable of a hypotonic stress-induced volume response that facilitates an increase in membrane permeability and the triggering of endogenous enzyme reactions. We describe a facile self-transformation process for constructing single- or multichambered molecularly crowded protocells based on the osmotic reconfiguration of lipid-coated coacervate droplets into multicompartmentalized coacervate vesicles. Hypotonic swelling broadens membrane permeability and increases transmembrane transport such that protease-based hydrolysis and enzyme cascades can be triggered and enhanced within the protocells by osmotically induced expansion. Specifically, we demonstrate how the enhanced production of nitric oxide (NO) within the swollen coacervate vesicles can be used to induce in vitro blood vessel vasodilation in thoracic artery rings. Our approach provides opportunities for designing reconfigurable model protocells capable of homeostatic volume regulation, dynamic structural reorganization, and adaptive functionality in response to changes in environment osmolarity, and could find applications in biomedicine, cellular diagnostics, and bioengineering.

A multicomponent digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults: A randomized controlled trial.

BACKGROUND: LGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults. METHODS AND FINDINGS: We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur. CONCLUSIONS: The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100053248.

Engineered Cytokine-Primed Extracellular Vesicles with High PD-L1 Expression Ameliorate Type 1 Diabetes.

Type 1 diabetes (T1D), which is a chronic autoimmune disease, results from the destruction of insulin-producing ß cells targeted by autoreactive T cells. The recent discovery that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) function as therapeutic tools for autoimmune conditions has attracted substantial attention. However, the in vivo distribution and therapeutic effects of MSC-EVs potentiated by pro-inflammatory cytokines in the context of T1D have yet to be established. Here, it is reported that hexyl 5-aminolevulinate hydrochloride (HAL)-loaded engineered cytokine-primed MSC-EVs (H@TI-EVs) with high expression of immune checkpoint molecule programmed death-legend 1 (PD-L1) exert excellent inflammatory targeting and immunosuppressive effects for T1D imaging and therapy. The accumulated H@TI-EVs in injured pancreas not only enabled the fluorescence imaging and tracking of TI-EVs through the intermediate product protoporphyrin (PpIX) generated by HAL, but also promoted the proliferative and anti-apoptotic effects of islet ß cells. Further analysis revealed that H@TI-EVs exhibited an impressive ability to reduce CD4+ T cell density and activation through the PD-L1/PD-1 axis, and induced M1-to-M2 macrophage transition to reshape the immune microenvironment, exhibiting high therapeutic efficiency in mice with T1D. This work identifies a novel strategy for the imaging and treatment of T1D with great potential for clinical application.

MiR-185-5p measurement assists in reflecting Th1/Th2 cell imbalance, inflammatory cytokine production, and exacerbation risk for childhood asthma.

BACKGROUND: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma. METHODS: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay. RESULTS: MiR-185-5p was increased in childhood asthma patients versus HCs [median (interquartile range (IQR)): 2.315 (1.770-3.855) versus 1.005 (0.655-1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1ß (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1ß or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070-4.905) versus 1.900 (1.525-2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010). CONCLUSION: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients.

Plasma metabolomics-based reveals the treatment mechanism of ShenGui capsule for application to coronary heart disease in a rat model.

Shen Gui capsule (SGC) has been demonstrated to have a significant treatment effect for coronary heart disease (CHD). Nevertheless, the holistic therapeutic mechanism of SGC in vivo remain poorly interpreted. We aimed to systematically explore the preventive effect and mechanism of SGC on CHD rats using plasma metabolomics strategy. Rat CHD model was established by left anterior descending coronary artery ligation (LAD). Echocardiography, histological analyses of the myocardium and biochemical assays on serum were used to confirm the successful establishment of the CHD model and therapeutic effects of SGC. Then, UHPLC-MS/MS-based plasma metabolomics was combined with multivariate data analysis to screen potential pharmaco biomarkers associated with SGC treatment in the LAD-induced rat CHD model. After SGC treatment, 12 abnormal metabolites considered as potiential pharmaco biomarkers recovered to near normal levels. These biomarkers were involved in several metabolic pathways, including fat and protein metabolism, phenylalanine metabolism, neuroactive ligand-receptor interaction, androgen receptor signaling pathway, and estrone metabolism.These results suggested that SGC achieves therapeutic action on CHD via regulating various aspects of the body such as energy metabolism, neurological disturbances and inflammation, and thus plays a significant role in the treatment of CHD and its complications. The study is useful to systematically understand and analyze the mechanism of SGC's "multipie pathways, multiple levels, multiple targets" prevention and treatment of CHD.

Latent profile analysis to identify subgroups of Chinese sexual minority adolescents at risk of suicidality.

BACKGROUND: This study aimed to identify latent class profiles of sexual minority adolescents (Men Sexually attracted to Men, Women Sexually attracted to Women, and Bisexual) with elevated suicidal ideation. METHODS: Data were collected from 18 secondary schools in China. Sub-group classifications were identified using variables associated with suicidal ideation in sexual minority adolescents, including parental relationship quality, electronic equipment time, school bullying, and sleep quality using the Chinese version of the Pittsburgh Sleep Quality Index to measure sleep. Anxiety was measured using the Generalized Anxiety Disorder 7 (GAD-7), depression was measured using the Patient Health Questionnaire 9 (PHQ-9), hypomania using the Hypomanic Checklist-32 (HCL-32), positive coping style was identified using the Trait Coping Style Questionnaire, and self-efficacy was measured by the General Self-Efficacy Scale. RESULTS: Four distinctive profiles were derived from the data. Compared to "low-risk" group (Class 3), the "adolescent with mood problems" group (Class 2) had a 9.81 times higher risk of suicidal ideation; the those who classified as "severe bullied adolescent" (Class 4) had a 9.26 times higher risk of suicidal ideation. and the "adolescents with low self-efficacy" group (Class 1) had a 4.48 times higher risk of suicidal ideation. CONCLUSIONS: Sexual minority adolescents with mood problems have the highest risk of suicidal ideation, followed by adolescents frequently being bullied at school. Interventions aimed at reducing suicide risk among sexual minority adolescents may benefit from attending to such profile factors identified in this study to develop targeted clinical care.

Giant Coacervate Vesicles As an Integrated Approach to Cytomimetic Modeling.

Although giant unilamellar vesicles (GUVs) have been extensively studied as synthetic cell-like microcompartments, their applicability as cytomimetic models is severely compromised by low levels of membrane permeability, low encapsulation efficiencies, and high physicochemical instability. Here, we develop an integrated cytomimetic model comprising a macromolecularly crowded interior with high sequestration efficiency and enclosed within a phospholipid membrane that is permeable to molecules below a molecular weight cutoff of ca. 4 kDa. The protocells are readily prepared by spontaneous assembly of a phospholipid membrane on the surface of preformed polynucleotide/polysaccharide coacervate microdroplets and are designated as giant coacervate vesicles (GCVs). Partial anchoring of the GCV membrane to the underlying coacervate phase results in increased robustness, lower membrane fluidity, and increased permeability compared with GUV counterparts. As a consequence, enzyme and ribozyme catalysis can be triggered in the molecularly crowded interior of the GCV but not inside the GUVs when small molecule substrates or inducers are present in the external environment. By integrating processes of membrane-mediated compartmentalization and liquid-liquid microphase separation, GCVs could offer substantial advantages as cytomimetic models, synthetic protocells, and artificial biomolecular microreactors.

Enhancing the Sensitivity of DNA and Aptamer Probes in the Dextran/PEG Aqueous Two-Phase System.

Increasing the local concentration of DNA-based probes is a convenient way to improve the sensitivity of biosensors. Instead of using organic solvents or ionic liquids that phase-separate with water based on hydrophobic interactions, we herein studied a classic aqueous two-phase system (ATPS) comprising polyethylene glycol (PEG) and dextran. Polymers of higher molecular weights and higher concentrations favored phase separation. DNA oligonucleotides are selectively enriched in the dextran-rich phase unless the pH was increased to 12. A higher volume ratio of PEG-to-dextran and a higher concentration of PEG also enrich more DNA probes in the dextran-rich phase. The partition efficiency of the T15 DNA was enriched around seven times in the dextran phase when the volume ratio of dextran and PEG reached 1:10. The detection of limit improved by 3.6-fold in a molecular beacon-based DNA detection system with the ATPS. The ATPS also increased the sensitivity for the detection of Hg2+ and adenosine triphosphate, although these target molecules alone distributed equally in the two phases. This work demonstrates a simple method using water soluble polymers to improve biosensors.

Dysfunction in Sertoli cells participates in glucocorticoid-induced impairment of spermatogenesis.

The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage-specific marker antigen F4/80 as well as inflammation-related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism-related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone-treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase-4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone-induced impairment of spermatogenesis.

Invasion and Defense Interactions between Enzyme-Active Liquid Coacervate Protocells and Living Cells.

The design and construction of mutual interaction models between artificial microsystems and living cells have the potential to open a wide range of novel applications in biomedical and biomimetic technologies. In this study, an artificial form of invasion-defense mutual interactions is established in a community of glucose oxidase (GOx)-containing liquid coacervate microdroplets and living cells, which interact via enzyme-mediated reactive oxygen species (ROS) damage. The enzyme-containing coacervate microdroplets, formed via liquid-liquid phase separation, act as invader protocells to electrostatically bind with the host HepG2 cell, resulting in assimilation. Subsequently, the glucose oxidation in the liquid coacervates initiates the generation of H2 O2 , which serves as an ROS resource to block cell proliferation. As a defense strategy, introduction of catalase (CAT) into the host cells is exploited to resist the ROS damage. CAT-mediated decomposition of H2 O2 leads to the ROS scavenging and results in the recovery of cell viability. The results obtained in the current study highlight the remarkable opportunities for the development of mutual interacting communities on the interface of artificial protocells/living cells. They also provide a new approach for engineering cellular behaviors through exploiting artificial nonliving microsystems.

A molecular device providing a remarkable spin filtering effect due to the central molecular stretch caused by lateral zigzag graphene nanoribbon electrodes.

Through the density functional theory, we studied molecular devices composed of single tetrathiafulvalene (TTF) molecules connected with zigzag graphene nanoribbon electrodes by four different junctions. Interestingly, some devices have exhibited half-metallic behavior and can bring out a perfect spin filtering effect and remarkable negative differential resistance behavior. The current-voltage characteristics show that these four devices possess different spin current values. We found that all the TTF molecules were stretched due to interactions with the electrodes in the four devices. This leads to the Fermi levels of the three devices being down-shifted to the valence band; therefore, these devices exhibit half-metallic properties. The underlying mechanisms of the different spin current values are attributed to the different electron transmission pathways (via chemical bonds or through hopping between atoms). These results suggest that the device properties and conductance are controlled by different junctions. Our work predicts an effective way for designing high-performance spin-injected molecular devices.

Accelerated kinetic Monte Carlo: A case study; vacancy and dumbbell interstitial diffusion traps in concentrated solid solution alloys.

Vacancy and self-interstitial atomic diffusion coefficients in concentrated solid solution alloys can have a non-monotonic concentration dependence. Here, the kinetics of monovacancies and ⟨100⟩ dumbbell interstitials in Ni-Fe alloys are assessed using lattice kinetic Monte Carlo (kMC). The non-monotonicity is associated with superbasins, which impels using accelerated kMC methods. Detailed implementation prescriptions for first passage time analysis kMC (FPTA-kMC), mean rate method kMC (MRM-kMC), and accelerated superbasin kMC (AS-kMC) are given. The accelerated methods are benchmarked in the context of diffusion coefficient calculations. The benchmarks indicate that MRM-kMC underestimates diffusion coefficients, while AS-kMC overestimates them. In this application, MRM-kMC and AS-kMC are computationally more efficient than the more accurate FPTA-kMC. Our calculations indicate that composition dependence of migration energies is at the origin of the vacancy's non-monotonic behavior. In contrast, the difference between formation energies of Ni-Ni, Ni-Fe, and Fe-Fe dumbbell interstitials is at the origin of their non-monotonic diffusion behavior. Additionally, the migration barrier crossover composition-based on the situation where Ni or Fe atom jumps have lower energy barrier than the other one-is introduced. KMC simulations indicate that the interplay between composition dependent crossover of migration energy and geometrical site percolation explains the non-monotonic concentration-dependence of atomic diffusion coefficients.

Control of patterns of symmetric cell division in the epidermal and cortical tissues of the Arabidopsis root.

Controlled cell division is central to the growth and development of all multicellular organisms. Within the proliferating zone of the Arabidopsis root, regular symmetric divisions give rise to patterns of parallel files of cells, the genetic basis of which remains unclear. We found that genotypes impaired in the TONNEAU1a (TON1a) gene display misoriented symmetric divisions in the epidermis and have no division defects in the underlying cortical tissue. The TON1a gene encodes a microtubule-associated protein. We show that in the ton1a mutant, epidermal and cortical cells do not form narrow, ring-like preprophase bands (PPBs), which are plant-specific, cytoskeletal structures that predict the position of the division plane before mitosis. The results indicate that in the cortex but not in the epidermis, division plane positioning and patterning can proceed correctly in the absence of both a functional TON1a and PPB formation. Differences between tissues in how they respond to the signals that guide symmetric division orientation during patterning might provide the basis for organised organ growth in the absence of cell movements.

Thermal stability and irradiation response of nanocrystalline CoCrCuFeNi high-entropy alloy.

Grain growth and phase stability of a nanocrystalline face-centered cubic (fcc) Ni0.2Fe0.2Co0.2Cr0.2Cu0.2 high-entropy alloy (HEA), either thermally- or irradiation-induced, are investigated through in situ and post-irradiation transmission electron microscopy (TEM) characterization. Synchrotron and lab x-ray diffraction measurements are carried out to determine the microstructural evolution and phase stability with improved statistics. Under in situ TEM observation, the fcc structure is stable at 300 °C with a small amount of grain growth from 15.8 to ∼20 nm being observed after 1800 s. At 500 °C, however, some abnormal growth activities are observed after 1400 s, and secondary phases are formed. Under 3 MeV Ni room temperature ion irradiation up to an extreme dose of nearly 600 displacements per atom, the fcc phase is stable and the average grain size increases from 15.6 to 25.2 nm. Grain growth mechanisms driven by grain rotation, grain boundary curvature, and disorder are discussed.

Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice.

1. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be very effective in hyperuricemic control. But it is poorly bioavailable after oral administration. Here, we determined the role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D. 2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity in vitro ATPase assay with a small EC50 value of 0.46 µM. 3. In the single-pass perfused mouse intestine model, the absorption of Pallidifloside D was not favored in the small intestine (duodenum, jejunum and ileum) with a P*w value of 0.35-0.78. By contrast, this compound was well-absorbed in the colon with a P*w value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum, ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of Pallidifloside D by a 2.5-fold after oral administration. 4. These results suggest that P-gp-mediated efflux is a limiting factor for intestinal absorption of Pallidifloside D in mice.

Lattice Distortion and Phase Stability of Pd-Doped NiCoFeCr Solid-Solution Alloys.

In the present study, we have revealed that (NiCoFeCr)100-xPdx (x= 1, 3, 5, 20 atom%) high-entropy alloys (HEAs) have both local- and long-range lattice distortions by utilizing X-ray total scattering, X-ray diffraction, and extended X-ray absorption fine structure methods. The local lattice distortion determined by the lattice constant difference between the local and average structures was found to be proportional to the Pd content. A small amount of Pd-doping (1 atom%) yields long-range lattice distortion, which is demonstrated by a larger (200) lattice plane spacing than the expected value from an average structure, however, the degree of long-range lattice distortion is not sensitive to the Pd concentration. The structural stability of these distorted HEAs under high-pressure was also examined. The experimental results indicate that doping with a small amount of Pd significantly enhances the stability of the fcc phase by increasing the fcc-to-hcp transformation pressure from ~13.0 GPa in NiCoFeCr to 20-26 GPa in the Pd-doped HEAs and NiCoFeCrPd maintains its fcc lattice up to 74 GPa, the maximum pressure that the current experiments have reached.