Adjuvant Efficacy of the ECMS-Oil on Immune Responses against Bordetella bronchiseptica in Mice through the TLR2/MyD88/NF-κB Pathway.

Bordetella infection can be efficiently prevented through vaccination. The current study investigated the effects of an extract of Cochinchina momordica seed (ECMS) combined with oil on the immune responses to the inactivated Bordetella vaccine in mice. Serum IgG and IgG1 level was significantly increased in ECMS-oil group compared to any other group (P < 0.05) 2 weeks after immunization, while groups ECMS200 µg/400 µg-oil had a markedly higher level of serum IgG2b and IgG3 than any other groups (P < 0.05). Moreover, lipopolysaccharide/ConA-stimulated proliferation of splenocytes was significantly enhanced in ECMS 400 µg-oil immunized mice in comparison with mice in any other group (P < 0.05). RT-PCR assay revealed that while ECMS800 µg-oil group had significantly higher levels of serum IL-4, IL-10, Toll-like receptor (TLR)2, and IL-1 beta than any other group (P < 0.05), the levels of serum IL-2, IL-4, and IL-10 were markedly increased in ECMS 400 µg-oil group as compared to any other groups (P < 0.05). Blood analysis showed that ECMS800 µg-oil and oil groups had a significantly higher number of immunocytes than any other groups (P < 0.05). There were significant differences in the number of IgG+, IgG2b+, and IgA+ cells in the lung between ECMS800 µg-oil group and any other groups (P < 0.05). Western blot analysis demonstrated that stimulation with ECMS 25 µg/mL or 50 ng/mL led to a significant increase in the expression of TLR2, MyD88, and NF-κB in Raw264.7 cells (P < 0.05). Compared with any other group, the expression of MyD88 was markedly increased in the cells stimulated with ECMS 50 ng/mL, as indicated by the RT-PCR analysis (P < 0.05). Overall, we observed that ECMS-oil efficiently enhanced the humoral or cellular immune responses against Bordetella and suggested that the mechanism of adjuvant activity of ECMS-oil might involve TLR2/MyD88/NF-κB signaling pathway.

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.

Low cryogenic mechanical loss composite silica thin film for low thermal noise dielectric mirror coatings.

Thermal noise in dielectric mirror-coatings is the limiting factor for ultra-high-precision metrologies employing optical cavities and being operated at cryogenic temperatures. Silica film is an indispensable low-refractive-index material for mirror coatings but suffers from high cryogenic mechanical loss and hence contributes to high thermal noise. We partitioned a thick silica film into thin layers by introducing blocking layers of titania. The cryogenic mechanical loss of silica was significantly suppressed; the effect was more profound for thinner partitions. Elimination of the transitions of the long-range two-level systems with scales that exceed the thickness of the silica partition is hypothesized. Dielectric mirror coatings with blocking layers are proposed to reduce the cryogenic thermal noise of the coatings. The calculated reflectance spectrum is consistent with that of the conventional quarter-wave (QW) stack around 1550 nm, and the calculated absorptance increases 2.2 times over that of a conventional titania/silica QW stack where the titania is absorptive.

Thickness-dependent crystallization on thermal anneal for titania/silica nm-layer composites deposited by ion beam sputter method.

Crystallization following thermal annealing of thin film stacks consisting of alternating nm-thick titania/silica layers was investigated. Several prototypes were designed, featuring a different number of titania/silica layer pairs, and different thicknesses (in the range from 4 to 40 nm, for the titania layers), but the same nominal refractive index (2.09) and optical thickness (a quarter of wavelength at 1064 nm). The prototypes were deposited by ion beam sputtering on silicon substrates. All prototypes were found to be amorphous as-deposited. Thermal annealing in air at progressive temperatures was subsequently performed. It was found that the titania layers eventually crystallized forming the anatase phase, while the silica layers remained always amorphous. However, progressively thinner layers exhibited progressively higher threshold temperatures for crystallization onset. Accordingly it can be expected that composites with thinner layers will be able to sustain higher annealing temperatures without crystallizing, and likely yielding better optical and mechanical properties for advanced coatings application. These results open the way to the use of materials like titania and hafnia, that crystallize easily under thermal anneal, but ARE otherwise promising candidate materials for HR coatings necessary for cryogenic 3rd generation laser interferometric gravitational wave detectors.