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Early integration of palliative care (PC) for patients with advanced cancer has been recommended to improve quality of care. This study aims to describe prevalence, temporal trend and predictors of PC use in metastatic breast cancer (mBCa) patients receiving critical care therapies (CCT; included invasive mechanic ventilation, percutaneous endoscopic gastrostomy tube, total parenteral nutrition, tracheostomy and dialysis). The National Inpatient Sample was queried for mBCa patients receiving CCT between 2005 and 2014. Annual percent changes (APC) were calculated for PC prevalence in the overall cohort and subgroups. Multivariable logistic analysis was used to explore predictors of PC use. Of 5833 mBCa patients receiving CCT, 880 (15.09%) received PC. Rate of PC use increased significantly from 2.53% in 2005 to 25.96% in 2014 (APC: 35.75%; p < 0.0001). Higher increase in PC use was observed in South (from 0.65% to 27.11%; APC: 59.42%; p < 0.0001), medium bedsize hospitals (from 3.75% to 26.05%; APC: 38.16%; p = 0.0006) and urban teaching hospitals (from 4.13% to 29.86%; APC: 37.33%; p = 0.0005). Multivariable analysis revealed that year interval, urban teaching hospitals, and invasive mechanical ventilation were associated with increased PC use, while primary diagnosis of gastrointestinal disorders, fractures, metastatic sites from lymph nodes and tracheostomy were associated with lower PC use. PC use in mBCa patients receiving CCT increases significantly over the period. However, it still remains low. Efforts to illustrate disparities in PC use are needed to improve quality of care for mBCa patients receiving CCT, especially for those hospitalized in rural and nonteaching hospitals. • Overall, 15.09% of mBCa patients with CCT receive inpatient PC. • Rate of inpatient PC use in mBCa patients receiving CCT increases significantly from 2005 to 2014. • This study highlights the underutilized PC in mBCa patients receiving CCT. • Future efforts to illustrate disparities in PC use are needed to improve quality of care. [ABSTRACT FROM AUTHOR]

Highlights • The typical trapezoid-shaped back-spall becomes an oval-shaped debris cloud finally. • There are three stages: the growth, the separation and the complete breakaway. • Special particle distributions and symmetric boundary can reduce time computation. • The Kernel Gradient Correction and fixed boundary can increase the accuracy. • An obvious slope in the inner fragments of the spall can be explained by gravity. Abstract Back-spalling of ceramic plates subjected to an impact is often observed phenomena, and a better understanding of back-spalling is critical for the design of protection systems. Numerical modeling is an effective means for modeling of structural failure caused by impacts. Among many numerical methods, Smoothed particle hydrodynamics (SPH) has advantages in handling these types of problems due to its features of meshfree, Lagrangian and particle. In this study, an experiment of Φ4.8 mm steel sphere impacting on an Al 2 O 3 ceramics plate at a speed of 767 m/s is performed. A high-speed camera is used to record the spalls ejected from the back side of the plate during frontal impacts. It is observed that the spall is typically trapezoid-shaped. To study the detailed process of the spalling and the formation of the shape of the back spall, a three-dimensional (3D) SPH is developed using the JC and JH-2 constitutive models. By analyzing some feature points and lengths and the outline of the experimental and numerical spall, it is found that the spalling process can be divided into 3 major stages during the impact event time of 55μs to 445μs: the growth of spall, the separation of spall from plate, and the complete breakaway of the spall from plate. It is also observed in the simulation that the z-component velocity of the lateral side is bigger than the that of the front arc salient. This difference would finally lead the spall to become an oval-shaped debris cloud, which is the same as showed in the experiment. Some typical cracks occur and propagate within the numerical model of the ceramic plate. In the present SPH code, variable space particle distributions are applied to reduce the computation time; and the Kernel Gradient Correction (KGC) is applied to increase the accuracy. The gravity field is considered in our SPH code to simulate the slope in the trajectory of the inner fragments of the spall, which is also observed in the experiment. These improvements in SPH lead to better agreement with the experimental observations on the spall features. [ABSTRACT FROM AUTHOR]

• A co-immobilization system of dual-enzyme and coenzyme was successfully constructed. • The immobilized enzymes presented improved stability and fine reusability. • The system realized chiral (R)−1-phenylethanol highly selective production and coenzyme effective recycling. Coenzymes are required in the reaction catalyzed by oxidoreductases. The research on coenzyme regeneration has always been a hot topic in the field of biological catalysis. In this work, we tried to construct a co-immobilization system of glucose dehydrogenase (GDH), (R)-1-phenylethanol dehydrogenase ((R)-PEDH) and coenzyme with functional magnetic nanoparticles as carriers, so as to realize chiral (R)-1-phenylethanol highly selective production and coenzyme effective recycling. The enzymatic properties of immobilized enzymes were explored. The results showed that the immobilized enzymes had improved stability and fine reusability. In addition, during the catalytic coupling reaction at a final concentration of 2.63 μM NAD+, the total turnover number (TTN) was as high as 924, and the volumetric productivity of (R)-1-phenylethanol was 37.06 mg·L−1·h−1. After reused for 10 cycles, the catalytic efficiency of immobilized coenzyme can still be maintained at more than 30%. From multiple perspectives, the immobilized dual-enzymes and coenzyme system seems to be a multifunctional system for (R)-1-phenylethanol production and coenzyme regeneration. [ABSTRACT FROM AUTHOR]

3-dimensional architectured polymers, for example, giant molecules, present distinct dynamics from chain-like polymers and are coarse-grained as soft-clusters. There is a critical number of beads, above which their melts cannot relax under thermal energy and become cooperative glass. To reveal the role of dispersity, we study the dynamics of binary blends of giant molecules with the same glass transition temperature by rheological experiments and by molecular dynamics simulations. The large component of the blend, OPOSS 24 or 141335, contains more beads than the critical number and forms cooperative glass, while the small component contains less beads than the critical number. The gradual change of volume fraction allows us to fine-adjust the average number of beads. An abrupt slowdown happens only if the volume fraction of the large component reaches 80%. Both experimental and simulated data can be described by a Vogel–Fulcher–Tammann-like equation against volume fractions with only one fitting parameter. The divergent relaxation times can also be rewritten as a function of the average number of beads. Such abrupt dynamic slowdown has to be induced by the glass-like cooperative dynamics. The cooperative glass state may only be reached when the majority of giant molecules or generally speaking, soft-clusters, are large enough. If we regard binary blends of soft-clusters as large and small cooperative rearranging regions, this may provide a direct approach to glass problems and may shed light on our understanding. [Display omitted] • Dynamics of binary blends of soft-clusters combining experiments and simulations. • Governing equations against volume fractions or the average number of beads. • The role of dispersity on cooperative glass, dominated by large soft-clusters. [ABSTRACT FROM AUTHOR]

To explore the mechanisms of diabetes mellitus (DM)-induced testicular injury caused by modulation of testicular glycolysis and gut microbiota (GM), and evaluation of the efficacy of catalpol in reversing testicular morbidity. A model of DM-induced testicular injury was established using a high-fat diet in KK-Ay mice. Microbial communities in the feces of mice in normal, model and catalpol (Cat) groups were analyzed by 16S gene sequencing. Correlations between the GM and lactate metabolism levels, lactate dehydrogenase activity, and indicators of testicular injury were analyzed. Cat significantly reduced general indicators of diabetes in mice with DM-induced reproductive injury, mitigated damage to the testicular tissue, and increased sperm count and motility. Additionally, the levels of products of glycolysis metabolism (e.g. lactate) increased following Cat treatment compared with the Model group. Disorders in the GM were also reversed in the Cat group. Cat ameliorated DM-induced testicular injury in KK-Ay mice by increasing the energy available to germ cells through glycolysis, principally through modulation of the GM and a reduction in the quantities of associated pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM)-induced reproductive damage is an important cause of infertility for male DM patients, we herein evaluated the effects of catalpol on diabetic reproductive damage through the suppression of the AGEs/RAGE/Nox4 signaling pathway. KK-Ay diabetic reproductive damage mice were administered with catalpol for 8 weeks, the testis/body weight ratio, testicular histopathology, the levels of endogenous hormone and the activity of testicular marker enzymes were determined. In vitro, the GC-2 cell injury model was induced by advanced glycation end-products (AGEs) and pretreated with catalpol. Cell viability, apoptosis, and oxidative stress markers were detected and the mechanism based on the AGEs/RAGE/Nox4 pathway was explored. Catalpol showed remarkable capacity on protecting diabetic reproductive damage by improving the histomorphology of the testes, increasing the testis/body weight ratio and activity of acid phosphatase (ACP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (γ-GT). The reduced testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in DM mice were also reversed with catalpol intervention. Moreover, catalpol showed markedly effects of anti-oxidative in vivo and in vitro, which significantly down-regulated reactive oxygen species (ROS) levels and restored superoxide dismutase (SOD) activity, meanwhile decreased GC-2 cell apoptosis and Bax/Bcl-2 ratio. Moreover, the over-expression of receptors for AGEs (RAGE), NADPH oxidase type 4 (Nox4) and phosphorylation of nuclear transcription factor-κB p65 (NF-κB p65) were suppressed by catalpol. Catalpol could alleviate DM-induced male reproductive damage by inhibiting oxidative stress-induced apoptosis and inflammation mediated by AGEs/RAGE/Nox4 signaling pathway. Unlabelled Image [ABSTRACT FROM AUTHOR]

Replacing carbon black and silica with organic fillers can reduce the weight of polymer nanocomposites. Soft-nanoparticles (SNPs), a type of organic filler, can be produced in large quantities through microemulsion polymerization. Their elasticities and diameters can be tuned for a wide range. This study aimed to investigate the linear viscoelasticity of athermal all-polystyrene nanocomposites with different molecular weights of matrix chains. Polymer nanocomposites filled with soft SNPs do not show this second plateau. But the second plateau is observed with semi-rigid SNPs if the weight percentage (φ) of SNPs is above a critical value φ c. Semi-rigid refers to the intermediate elasticity compared to phenol-capped silica nanoparticles and long-chain grafted silica nanoparticles/soft SNPs. In both cases of all-polystyrene nanocomposites, the entanglement plateau and higher frequency regions remain the same. This hints that polymer chains do not thread the network. Flory-Rehner theory further confirms negligible swelling of long polymer chains into dense crosslinking networks of SNPs. The modulus of this plateau scales to the 3.8 power of φ and the 0.26 power of M w. The critical weight percentage φ c for the onset of the second plateau corresponded with the compression of the polymer coil between two SNPs. As φ increases above φ c , polymer chains would be depleted from neighboring SNPs, resulting in this network of semi-rigid SNPs. Thus, we believe that the second plateau originated from this network. This study analyzed the second plateau and highlighted the variety of viscoelastic features associated with the elasticity of SNPs filled in polymer nanocomposites. [Display omitted] • The network of semi-rigid (without swelling) SNPs is formed by depleting polymers and leads to the second plateau. • The modulus of this plateau scales to the 3.8 power of the weight fraction of SNPs and the 0.26 power of Mw. • The onset of the second plateau corresponded with the squeeze of the polymer coil between neighboring SNPs. [ABSTRACT FROM AUTHOR]

Catalpol is an iridoid glycoside compound isolated from the root of Rehmannia glutinosa , which has been reported to be a promising candidate for the treatment of diabetic diseases. The present study aimed at investigating the effects and potential mechanism of catalpol on endothelial dysfunction and inflammation in diabetic nephropathy (DN). We constructed DN mice and advanced glycation end products (AGEs)-induced mouse glomerular endothelial cells (mGECs) injury model. The results demonstrated that catalpol effectively improved renal pathology and decreased levels of urine protein, serum creatinine, and blood urea nitrogen in DN mice. Catalpol significantly reduced endothelial dysfunction and inflammatory infiltration of macrophages in DN mice and AGEs-induced mGECs. To further study the protective mechanism of catalpol, we transfected DN mice with recombinant adeno-associated virus expressing receptor of AGEs (RAGE) and intervened AGEs-induced mGECs with inhibitors. Catalpol reversed endothelial dysfunction and inflammation aggravated by RAGE overexpression in DN mice. Meanwhile, catalpol significantly inhibited the RAGE/Ras homolog gene family member A (RhoA)/Rho-associated kinase (ROCK) pathway in DN mice with RAGE overexpression. Moreover, the combination of catalpol with inhibitors of RAGE, RhoA and ROCK exerted stronger anti-endothelial dysfunction and anti-macrophage infiltration effects on AGEs-induced mGECs compared with catalpol alone. In short, this study indicated that catalpol could ameliorate endothelial dysfunction and inflammation via suppression of RAGE/RhoA/ROCK pathway, hereby delaying the progression of DN. [Display omitted] • Catalpol ameliorates glomerular endothelial dysfunction and inflammation in DN. • RAGE overexpression in DN mice aggravates glomerular endothelial dysfunction and inflammatory infiltration of macrophages. • Catalpol inhibits AGEs-RAGE and its downstream RhoA/ROCK signaling pathway. [ABSTRACT FROM AUTHOR]

Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway. Log and Cat alone or in combination mitigated diabetic symptoms, decreased the level of fasting blood glucose, and increased that of serum insulin. The two drugs alone or in combination protected renal function from damage, prevented extracellular matrix hyperplasia and glycogen deposition, as well as alleviated the loss of podocytes detected by histological assay and immunohistochemistry. Flow cytometry revealed that Log and Cat alone or in combination relieved the apoptosis of AGEs-induced podocytes in vitro. Silencing RAGE by RNA interference played a protective role in podocyte apoptosis, whereas overexpression of it worked oppositely. Western blot exhibited that Log and Cat alone or in combination inhibited the activation of RAGE/p38 MAPK/p65 NF-κB and RAGE/Nox4/p65 NF-κB pathways in podocytes. The inhibitory effects of drug combination were more evident than those of individual treatments. Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4. [ABSTRACT FROM AUTHOR]