Eu3+ Single-Doped Phosphor with Antithermal Quenching Behavior and Multicolor-Tunable Properties for Luminescence Thermometry.

To date, non-contact luminescence thermometry methods based on fluorescence intensity ratio (FIR) technology have been studied extensively. However, designing phosphors with high relative sensitivity (Sr) has become a research hotspot. In this work, Eu3+ single-doped Ca2Sb2O7:Eu3+ phosphors with a high Sr value for dual-emitting-center luminescence thermometry are developed and proposed. The anti-thermal quenching behavior of Eu3+ originating from the energy transfer (ET) of host → Eu3+ is found and proved in the designed phosphors. Interestingly, adjustable color emission from blue to orange can be achieved. Surprisingly, the degree of the anti-thermal quenching behavior of Eu3+ gradually reduces from 240 to 127% as the Eu3+ doping content increases from 0.005 to 0.05 mol, attributed to most Eu3+ being located in the low symmetrical [Ca1O8] dodecahedral site. According to the differentiable responses of the host and Eu3+ to temperature, the maximal Sr value reaches 3.369% K-1 (383 K). Moreover, the ambient temperature can be intuitively predicted by observing the emitting color. Owing to the excellent performance in optical thermometry, color-tunable properties, and outstanding acid and alkali resistance for polydimethylsiloxane (PDMS) films, the developed Eu3+ single-doped Ca2Sb2O7:Eu3+ phosphors are expected to be prospective candidates in luminescence thermometers and LED devices in various conditions.

Evaluation of allergenicity of cow milk treated with enzymatic hydrolysis through a mouse model of allergy.

Cow milk (CM) allergy is a worldwide concern. Currently, few studies have been performed on the immunoreactivity of CM and fewer still on the antigenicity of CM in vivo and in vitro. In this study, we assessed the potential allergenicity of enzymatically hydrolyzed CM using in vitro ELISA and oral sensitization and challenge of BALB/c mice. Alcalase-, Protamex-, and Flavourzyme-treated CM (all from Novozymes) diminished IgE binding capacity, with greatest reductions of 56.31%, 50.62%, and 56.45%, respectively. Allergic symptoms and levels of total IgG1 were reduced, and allergic inflammation of the lung, jejunum, and spleen was relieved. Moreover, the numbers of CD8+ T and B220+ cells decreased, and the balance of CD4+ T/CD8+ T cells was effectively regulated. These findings suggest that the potential allergenicity of CM was reduced by enzymatic hydrolysis, and our research will lay a solid foundation for developing high-quality hypoallergenic CM products.

Evaluation of antigenicity and nutritional properties of enzymatically hydrolyzed cow milk.

While enzymatic hydrolysis is an effective method for lowering the antigenicity of cow milk (CM), research regarding the antigenicity and nutritional traits of CM hydrolysate is limited. Here, we evaluated the protein content, amino acid composition, sensory traits, color, flow behavior, and antigenicity of CM following enzymatic hydrolysis. The results showed that enzymatic hydrolysis increased the degree of hydrolysis, destroyed allergenic proteins, including casein, ß-lactoglobulin, and ɑ-lactalbumin, and significantly increased the content of free amino acids and nutritional quality. In particular, the antigenicity of CM was significantly reduced from 44.05 to 86.55% (P < 0.5). Simultaneously, the taste, color, and flow behavior of CM were altered, the sweetness and richness intensity decreased significantly (P < 0.5), and astringency and bitterness were produced. A slightly darker and more yellow color was observed in CM hydrolysate. In addition, apparent viscosity decreased and shear stress significantly increased with increasing shear rate intensity. The results will provide a solid theoretical foundation for the development of high-quality hypoallergenic dairy products.

Effects of enzymatic hydrolysis on the allergenicity of natural cow milk based on a BALB/c mouse model.

Cow milk allergy is one of the most prevalent food allergies worldwide, particularly in infants and children. To the best of our knowledge, minimal research exists concerning the antigenicity of cow milk (CM). This study was performed to evaluate the allergenicity of enzymatically hydrolyzed cow milk (HM) in a BALB/c mouse model. The mice were randomly divided into 5 groups (n = 12/group), which were sensitized with phosphate-buffered saline, CM, and HM (Alcalase-, or Protamex-, or Flavorzyme-treated cow milk; Novo Nordisk; AT, PT, FT, respectively), respectively, using cholera toxin as adjuvant on d 0, 7, 14, 21. On d 28, the test mice were orally challenged with phosphate-buffered saline, CM, and HM (AT, PT, or FT) alone. Anaphylactic symptoms were monitored in the mice. Antibody, cytokine, histamine, and mouse mast cell protease-1 (mMCP-1) levels were measured using enzyme-linked immunosorbent assays. In addition, the numbers of T helper (Th)1 and Th2 cells, as well as the proportions of CD4+CD25+Foxp3+ Treg cells, in mouse spleens were detected using flow cytometry. Statistical significance was determined by one-way ANOVA. The results revealed significant differences between CM- and HM-challenged mice. Among these, the clinical scores of HM-challenged mice (AT, 1.50; PT, 2.00; FT, 1.92) were lower than those of CM-challenged mice (positive control, 2.83), but body weight and temperature of HM-challenged mice were higher than those of CM-challenged mice. In addition, significant reductions of allergen-specific IgE, IgG, histamine, and mMCP-1 were showed in HM-challenged mice, especially for histamine, ranging from 171.42 ng/mL to 214.94 ng/mL. Remarkable reductions of IL-4, IL-5, and IL-13 levels, as well as elevations of interferon-γ and IL-10 levels in the spleens of HM-challenged mice were also detected. Moreover, the number of Th2 cells decreased in the HM-challenged mice, to 2.36% (AT), 1.79% (PT), and 4.03% (FT), respectively, whereas the numbers of Th1 cells (AT, 6.30%; PT, 6.70%; FT, 6.56%) and the proportions of CD4+CD25+Foxp3+Tregs (AT, 8.86%; PT, 9.21%; FT, 9.16%) increased significantly. Our findings indicate that exposure to HM was sufficient to induce a shift toward a Th1 response, thereby reducing potential allergenicity. Importantly, these results will lay a theoretical foundation for the development of hypoallergenic CM products.

Design and synthesis of new disubstituted benzoxazolone derivatives that act as iNOS inhibitors with potent anti-inflammatory activity against LPS-induced acute lung injury (ALI).

Acute lung injury (ALI) is a pulmonary disease that acts as a severe acute inflammatory response with no specific drugs. iNOS, a catalyst of the excessive production of NO, has been demonstrated to participate in the inflammatory process, and targeting iNOS may be a promising therapeutic pathway to alleviate ALI. In our research, eighteen new disubstituted benzoxazolone derivatives were synthesized, characterized, and evaluated for activity against NO production in an LPS-induced RAW264.7 cell. The results showed that these compounds could obviously inhibit the over-generation of NO and disubstitution at the 4, N-position of the benzoxazolone ring, presenting better potency than substitution only at the 4-position. Among the analogues generated, compounds 2c, 2d, and 3d showed NO inhibitory activity with IC50 values of 16.43, 14.72, and 13.44 µM and iNOS inhibitory activity with IC50 values of 4.605, 3.342, and 9.733 µM, respectively. Meanwhile, compounds 2c, 2d, and 3d could also inhibit the release of IL-6, IL-1ß in vitro and suppress xylene-induced ear edema in vivo to realize anti-inflammatory activity. Furthermore, compound 2d could significantly protect the LPS-induced ALI, presenting as decreased inflammatory cytokines and obvious pathological changes. Immunohistochemistry and molecular modeling demonstrated that compound 2d significantly inhibited the expression of iNOS in vivo and interacted with iNOS through two hydrogen bindings with the MET368 and ILE195 residues of the iNOS protein. These results demonstrated that compound 2d could be a promising lead structure for iNOS inhibitors, with anti-inflammatory activity to treat LPS-induced acute lung injury.

Donkey milk inhibits triple-negative breast tumor progression and is associated with increased cleaved-caspase-3 expression.

Donkey milk is considered an ideal substitute for human milk and is considered a potential complementary dairy product for the treatment of a variety of human diseases, including cancer. The purpose of this study was to investigate the inhibitory effect of donkey colostrum (DC) and mature milk (DM) on 4T1 triple-negative breast cancer (TNBC) tumors in mice. Metabolomics analyses showed that a total of 476 possible metabolites were found in both types of milk. Among them, 34 differential metabolites were identified, including 25 up-regulated and 9 down-regulated metabolites in the DC compared with DM. Both DC and DM are rich in many known anticancer constituents. The inhibitory effects of DC and DM on 4T1 primary tumors and the relative organ weight of the liver and lungs were determined by measuring the volume of primary tumors and weighing the liver and lungs. Both DC and DM significantly reduced both the primary tumor size and relative organ weight of the liver and lungs in 4T1 mice without affecting the bodyweight of mice. When the expression of cleaved caspase-3, Bax, and MMP2 was investigated by immunohistochemistry, the results showed that DC and DM inhibited the progression of 4T1 tumors by inducing the expression of cleaved-caspase-3 and Bax, and inhibiting the expression of MMP2 and CD31. Our data suggest that DC and DM inhibit the growth and metastasis of mouse 4T1 tumors by inducing apoptosis.