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Currently, considerable attention has been directed towards the significant role of the interphase in dictating the mechanical properties of composites. Herein, the mechanical behavior of SiC f /SiC composites with two distinct interphases, BN and BN/SiC, was delved into under a three-point bending. Meanwhile, analyses of the damage process and failure mechanism of the composites were conducted using acoustic emission (AE), digital image correlation (DIC), and dynamic mechanical analysis (DMA) methods. The results demonstrated the moderate interfacial bond strength of composites with BN/SiC interphase. Cracks were observed to be repeatedly deflected at the matrix/SiC interphase and fiber/BN interphase, leading to a larger bending strength and a pseudoplastic fracture mode. Ultimately, shear forces led to the failure of the composites. Overall, this study indicates that damage analysis provides a theoretical basis for comprehending potential damage in composites and optimizing interphase design. • Multi-scale analysis of damage mechanisms using non-destructive testing. • The crack deflection mechanisms of different interphases were analyzed. • The correlation of AE, DIC and DMA test methods in damage monitoring was established. [ABSTRACT FROM AUTHOR]

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1 – 3), along with nine known ones (4 – 12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H 2 O 2 -induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1 , 3 – 5 , and 7 showed a potent neuroprotective effect at 25 or 50 μM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse. [Display omitted] [ABSTRACT FROM AUTHOR]

The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver tumors in mice. We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr −/−mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE −/− mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured. C57BL/6J mice on HCD and ApoE −/− mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE −/− mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell–activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr −/− mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr −/− mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs. Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC. [ABSTRACT FROM AUTHOR]

Twenty-six clerodane diterpenoids have been isolated from T. sagittata , a plant species of traditional Chinese medicine Radix Tinosporae , also named as " Jin Guo Lan ". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1 – 8), and 18 known diterpenoids (9 – 26). The absolute configurations of compounds 1 , 2 , 5 , 8 , 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ -lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2 , 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC 50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 μM, respectively. These activities were significantly higher than that of the positive control minocycline (IC 50 = 23.57 ± 0.92 μM). Moreover, compounds 2 , 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF- α , IL-1 β and IL-6 that were increased by LPS stimulation. Twenty-six clerodane diterpenoids including eight undescribed ones were isolated from Tinospora sagittata (Oliv.) Gagnep, and some of them exhibited potent anti-neuroinflammatory activity. [Display omitted] • 8 undescribed clerodane diterpenoids were isolated from Tinospora sagittata. • Compound 1 is the first example of clerodane diterpenoid with a γ -lactone ring constructed between C-11 and C-17. • 3 compounds showed excellent inhibitory activity on NO production. • 2 compounds can reduce the expressions of iNOS, COX-2, TNF-α, IL-1 β and IL-6. [ABSTRACT FROM AUTHOR]

Precursor infiltration and pyrolysis (PIP) and chemical vapor infiltration (CVI) were used to fabricate SiC/SiC composites on a four-step 3D SiC fibre preform deposited with a pyrolytic carbon interface. The effects of fabrication processes on the microstructure and mechanical properties of the SiC/SiC composites were studied. Results showed the presence of irregular cracks in the matrix of the SiC/SiC composites prepared through PIP, and the crystal structure was amorphous. The room temperature flexural strength and modulus were 873.62 MPa and 98.16 GPa, respectively. The matrix of the SiC/SiC composites prepared through CVI was tightly bonded without cracks, the crystal structure had high crystallinity, and the room temperature bending strength and modulus were 790.79 MPa and 150.32 GPa, respectively. After heat treatment at 1300 °C for 50 h, the flexural strength and modulus retention rate of the SiC/SiC composites prepared through PIP were 50.01% and 61.87%, and those of the composites prepared through CVI were 99.24% and 96.18%, respectively. The mechanism of the evolution of the mechanical properties after heat treatment was examined, and the analysis revealed that it was caused by the different fabrication processes of the SiC matrix. After heat treatment, the SiC crystallites prepared through PIP greatly increased, and the SiO x C y in the matrix decomposed to produce volatile gases SiO and/or CO, ultimately leading to an increase in the number of cracks and porosity in the material and a decrease in the material load-bearing capacity. However, the size of the SiC crystallites prepared through CVI hardly changed, the SiC matrix was tightly bonded without cracks, and the load-bearing capacity only slightly changed. [ABSTRACT FROM AUTHOR]

We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (K D) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin. Image 1 • Amide-sialoside tailored protein was prepared as mucin mimic. • The neomucins showed influenza virion adsorbent capability. • The synthetic glycoconjugates can inhibit hemagglutinin and neuraminidase activity. [ABSTRACT FROM AUTHOR]

A triazolylsialoside-human serum albumin conjugate was prepared as a multivalent hemagglutinin and neuraminidase inhibitor using a di-(N -succinimidyl) adipate strategy. Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) indicated that five tetravalent sialyl galactosides were grafted onto the protein backbone resulting in an eicosavalent triazolylsialoside-protein complex. Compared with monomeric sialic acid, molecular interaction studies showed that the synthetic pseudo-glycoprotein bound tightly not only to hemagglutinin (HA)/neuraminidase (NA) but also to mutated drug-resistant NA on the surface of the influenza virus with a dissociation constant (K D) in the 1 μM range, attributed to the cluster effect. Moreover, this glycoconjugate exhibited potent antiviral activity against a broad spectrum of virus strains and showed no cytotoxicity towards Human Umbilical Vein Endothelial Cells (HUVECs) and Madin-Darby canine kidney (MDCK) cells at high concentrations. Further mechanistic studies demonstrated this multivalent sialyl conjugate showed strong capture and trapping of influenza virions, thus disrupting the ability of the influenza virus to infect host cells. This research lays the experimental foundation for the development of new antiviral agents based on multivalent sialic acid-protein conjugates. [Display omitted] • An eicosavalent triazolylsialoside bovine serum albumin conjugate was prepared. • The conjugate acts as dual influenza hemagglutinin/neuraminidase inhibitor. • The sialoside has the ability to aggregate influenza virion particles. [ABSTRACT FROM AUTHOR]

We describe the preparation of thiosialoside-modified poly (methyl vinyl ether- alt -maleic anhydride) as second-generation polymeric conjugates for the inhibition of influenza virus infection. These synthetic glycopolymers show significantly enhanced neuraminidase inhibitory and antiviral activity in enzyme and cellular levels, respectively. The polyvalent thiosialosides also exhibit comparable inhibitory activity to the first-line anti-influenza drugs Zanamivir® and Oseltamivir® against the PR8 influenza virus strain in virus growth inhibition assays, which may be attributed to multivalent binding to neuraminidase on the virion particles, leading to the virion aggregation and further inhibiting the attaching/fusion and releasing steps in the influenza virus life-cycle. These findings suggest that attaching monomeric sialoside with neuraminidase inhibitory activity to a polymeric scaffold will synergistically disturb both the early and late stages of influenza virus infection, and provides a basis for the development of efficacious anti-viral agents against both wild-type and drug-resistant mutant strains. Image 1 • Second-generation thiosialoside tailored polymers were prepared. • The synthetic glycopolymers showed comparable NA inhibitory activity with Zanamivir. • Early binding/fusion and late releasing stages of influenza infection were inhibited. [ABSTRACT FROM AUTHOR]