Advancements in lipid-based delivery systems for functional foods: a comprehensive review of literature and patent trends.

Lipid-based delivery systems (LDS) have emerged as cornerstone techniques for bolstering the bioavailability of lipophilic bioactive compounds, addressing challenges related to solubility, stability, and absorption. This critical review examined a substantial dataset of 6,907 scientific articles and 3,021 patents from 2001-2023, elucidating the multifaceted evolution of LDS, with a particular focus on its industrial and patent-driven perspective. Notably, there were pronounced surges in functional food patent applications in 2004, 2011, and 2019. The trajectory revealed a shift from foundational nanoemulsions to more complex structures, such as double/multiple emulsions, solid lipid nanoparticles, Pickering emulsions, and bigels. The review further identified the top 10 leading institutions shaping this domain. Technologies like spray-drying, microfluidics, and phase gelation had revolutionized the landscape, resulting in refined sensory experiences, innovative reduced-fat formulations, enriched beverages, tailor-made infant nutrition, and nuanced release mechanisms for flavors. The review also spotlighted current research frontiers, notably Pickering emulsions, bigels, and multiple emulsions. These emerging technologies not only exemplified the ongoing innovation in the field but also underscored their potential in reshaping the future landscape of value-added functional foods.

Recent advances in self-assembly behaviors of prolamins and their applications as functional delivery vehicles.

Prolamins are a group of storage proteins (zeins, kafirins, hordeins, secalins, gliadins, glutenins, and avenins) found in the endosperm of cereal grains and characterized by high glutamine and proline content. With the high proportion of nonpolar amino acids (40-80%) and peculiar solubility (alcohol (60-90%), acetic acid, and alkaline solutions), prolamins exhibit tunable self-assembly behaviors. In recent years, research practices of utilizing prolamins as green building materials of functional delivery vehicles to improve the health benefits of bioactive compounds have surged due to their attractive advantages (e.g. sustainability, biocompatibility, fabrication potential, and cost-competitiveness). This article covers the recent advances in self-assembly behaviors leading to the fabrication of nanoparticles, fibers, and films in the bulk water phase, at the air-liquid interface, and under the electrostatic field. Different fabrication methods, including antisolvent precipitation, evaporation induced self-assembly, thermal treatment, pH-modulation, electrospinning, and solvent casting for assembling nanoarchitectures as functional delivery vehicles are highlighted. Emerging industrial applications by mapping patents, including encapsulation and delivery of bioactive compounds and probiotics, active packaging, Pickering emulsions, and as functional additives to develop safer, healthier, and sustainable food products are discussed. A future perspective concerning the fabrication of prolamins as advanced materials to promote their commercial food applications is proposed.

HPCAL1 promotes glioblastoma proliferation via activation of Wnt/ß-catenin signalling pathway.

Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca2+ ) can positively regulate the initiation of malignancy with regard to GBM by modulating quiescence, proliferation, migration and maintenance. Hippocalcin like-1 protein (HPCAL1) serves as a sensor of Ca2+ . However, the understanding of HPCAL1 activity in GBM is limited. The present study revealed that the gene HPCAL1 was up-regulated by Ca2+ in the tissues and cells of GBM. Ectopic expression of HPCAL1 promoted proliferation of cells. Exhaustion of HPCAL1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL1 enhanced the Wnt pathway by stimulating ß-catenin accumulation and nuclear translocation in GBM cells, while ß-catenin silencing significantly inhibited the proliferation and growth of the GBM cells. Our results showed that Ser9 phosphorylation of GSK3ß was significantly decreased after HPCAL1 knockdown in GBM cells, and knockdown of the gene GSK3ß in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND1 and c-Myc. Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL1 knockdown, while it was promoted via overexpression of HPCAL1. The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL1 and impaired transcription of the genes c-Myc and CCND1. These studies elucidate the tumour-promoting activity of HPCAL1. They also offer an innovative therapeutic strategy focusing on the HPCAL1-Wnt/ß-catenin axis to regulate proliferation and development of GBM.

Specific dephosphorylation of Janus Kinase 2 by protein tyrosine phosphatases.

Many protein kinases are activated through phosphorylation of an activation loop thereby turning on downstream signaling pathways. Activation of JAK2, a nonreceptor tyrosine kinase with an important role in growth factor and cytokine signaling, requires phosphorylation of the 1007 and 1008 tyrosyl residues. Dephosphorylation of these two sites by phosphatases presumably inactivates the enzyme, but the underlying mechanism is not known. In this study, we employed MALDI-TOF/TOF and triple quadrupole mass spectrometers to analyze qualitatively and quantitatively the dephosphorylation process by using synthetic peptides derived from the tandem autophosphorylation sites (Y1007 and Y1008) of human JAK2. We found that tyrosine phosphatases catalyzed the dephosphorylation reaction sequentially, but different enzymes exhibited different selectivity. Protein tyrosine phosphatase 1B caused rapid dephosphorylation of Y1008 followed by Y1007, while SHP1 and SHP2 selectively dephosphorylated Y1008 only, and yet HePTP randomly removed a single phosphate from either Y1007 or Y1008, leaving behind mono-phosphorylated peptides. The specificity of dephosphorylation was further confirmed by molecular modeling. The data reveal multiple modes of JAK2 regulation by tyrosine phosphatases, reflecting a complex, and intricate interplay between protein phosphorylation and dephosphorylation.

Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay.

Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. Quantitative analysis of CYP expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. At present, chemical probe-based assay is the most widely used approach for the evaluation of CYP activity although there are cross-reactions between the isoforms with high sequence homologies. Therefore, quantification of each isozyme is highly desired in regard to meeting the ever-increasing requirements for carrying out pharmacokinetics and personalized medicine in the academic, pharmaceutical, and clinical setting. Herein, an absolute quantification method was employed for the analysis of the seven isoforms CYP1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1 using a proteome-derived approach in combination with stable isotope dilution assay. The average absolute amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0, 4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1, respectively. Importantly, the expression level of CYP3A4 showed high correlation (r = 0.943, p < 0.0001) with the functional activity, which was measured using bufalin-a highly selective chemical probe we have developed. The combination of MRM identification and analysis of the functional activity, as in the case of CYP3A4, provides a protocol which can be extended to other functional enzyme studies with wide application in pharmaceutical research.

Optimal design and 3D printing of prosthetic socket based on the interface pressure between the socket and residual limb.

BACKGROUND: At present, the quantifiable pressure distribution at the interface between the socket and stump is seldom applied in the design and fabrication of the socket. OBJECTIVES: This study aimed to optimize the socket based on the interface pressure of residual limb-socket, thereby avoiding excessive local load on the residual limb, reducing the load on the pressure-sensitive (PS) regions and making the limb more evenly loaded. METHODS: The residual limb was divided into the main load-bearing regions, the pressure-tolerant regions, and the PS regions according to the carrying capacity at its different regions. Based on these bearing regions, a mathematical function was developed, which applied modifications/adjustments to the socket design in a Computer Aided Design (CAD) environment by using the adjustment function. Besides, three adjusted sockets were produced by using selective laser sintering 3D printing technology. RESULTS: The wearing of the 3D-adjusted printed sockets reduced the contact interface pressures in the distal tibial region and the fibular head region by 85.6% and 84.4%, respectively. In addition, the walking distance of the subject was increased by 18.34%, and the overall pressure distribution on the stump became more uniform. CONCLUSIONS: The pressures in the original overpressure regions and the PS regions could reduce, whereas the pressure in the low-load regions of main load-bearing or pressure-tolerant regions could increase by modifying the socket with the pressure adjustment function. At the same time, the pressure among different regions was more uniform except for the sensitive regions.

[Artificial selection for cattle based on high-density SNP markers].

With the implementation of genetic improvement in recent years, artificial selection has greatly improved beef cattle production performance and its genetic basis has been dramatically changed. In this study, based on the Illumina BovineSNP50 (54K) and BovineHD (770K) BeadChip and the FST value, we analyzed the genetic differentiation of cattle and screened the imprints of selection in bovine genome. Finally, we found 47104 OUTLIER SNP loci and 3064 candidate genes, for example, CLIC5, TG, CACNA2D1, and FSHR etc. The biological processes and molecular functions of genes were analyzed through gene annotation.The results of this study established a genome-wide map of selection footprints in beef cattle genome and a clue for in-depth study of artificial selection and understanding of biological evolution.Our results indicate that artificial selection has played an important role in cattle breed genetic improvement.

Study on friction behavior at the interface between prosthetic socket and liner.

PURPOSE: The friction characteristics at the interface between prosthetic socket and liner have an important influence on the walking function and wearing comfort of amputees. The frictional behavior at the prosthetic socket/liner interface can provide theoretical guidance for the design and selection of prosthetic materials. So it is of great significance to study the friction behavior at prosthetic socket/liner interface. METHODS: The surface roughnesses of the prosthetic socket and liner materials were measured by a laser confocal microscope. The frictional behavior at the prosthetic socket/liner interface was studied on a UMT TriboLab Tribometer by simulating the reciprocating sliding contact mode. An infrared camera was used to take thermal images and then calculated the temperature increase at the socket/liner interface. RESULTS: The coefficient of friction of the silicon rubber fabric are significantly smaller than that of the foam liner materials. The frictional energy dissipation at the liner/acrylic socket interface is the smallest, while it is greater for 3D-printed socket materials. Meanwhile, the temperature increase has a positive correlation to the coefficient of friction and frictional energy dissipation. CONCLUSIONS: The three kinds of 3D-printed materials with high surface roughness have higher interface coefficient of friction and energy dissipation than acrylic material. The stiffness and energy consumption play an important role in the interface friction characteristics of the prosthetic liner materials. The appropriate coefficient of friction at the surface between prosthetic socket and liner is essential. A type of the reinforcement fiber has influence on the friction behavior of the 3D-printed reinforced nylon.

Soundscape Evaluation Comparison of Outdoor Activity Space Between Gated and Open Communities.

In communities, outdoor activity space is utilized most often by older adults and children, and the soundscape is very important for its quality. For different community planning modes, such as gated and open communities, focus should be on different soundscape enhancement strategies for outdoor spaces. In this paper, typical samples of activity spaces in a gated community and in an open community were used. The comparison was conducted through soundscape evaluation including an analysis of the dominance of various sound sources, noise annoyance, and the perceptual dimensions of soundscape. The results showed that noise annoyance in the gated community was significantly lower than in the open community, although the noise level was of no significance between the two communities. The community planning mode moderated the relationships among the soundscape perception parameters between the gated and open communities. To reduce noise annoyance in the gated communities, each sound source should be considered; in open communities, traffic noise only should be considered. In a gated community, adding natural sounds to reduce noise annoyance may be a feasible intervention; in an open community, this is not necessary. Besides, there was no relationship between noise annoyance and Eventfulness in an open community, indicating that noise annoyance was insufficient to explain the complex sound environment of the community. China's community planning will gradually shift from a gated community to an open community, making the soundscape of outdoor activity spaces likely to change dramatically in the future. The findings will help urban designers and managers to adopt targeted strategies to improve the soundscape and quality of life of community-dwelling older adults and children.

[The skin frictional properties of 4 kinds of commonly used prosthetic materials].

Skin frictional properties of four kinds of prosthetic materials in common use have been researched. Experiments are carried out on residual limb and on normal tibia. Surface roughness and the hydrophobic/hydrophilic of the skin and materials are also tested. Under normal load 0.3 N and 0.7 N, the friction coefficient of silicon rubber and skin has the maximum value among all the materials due to the surface property of silicon rubber (containing oil). There is remarkable difference in friction coefficient between normal skin and amputee skin when they are in contact with silicon rubber (P<0.05). Other materials show "the higher the hydrophobia tendency of surface, the lower the friction coefficient". There are no significant differences (P>0.05) in friction coefficient between amputee skin and normal skin when they are in contact with all materials under normal load 8 N.

One-pot synthesis of the CuNCs/ZIF-8 nanocomposites for sensitively detecting H2O2 and screening of oxidase activity.

The fluorescent CuNCs/ZIF-8 nanocomposites were facilely prepared by mixing the PEI protected CuNCs with the precursors of ZIF-8, and characterized by UV-vis absorption, fluorescence, FT-IR, TEM, XRD and XPS. The quantum yield of the CuNCs/ZIF-8 is 15 times that of the PEI-CuNCs. Furthermore, the CuNCs/ZIF-8 possesses better stability and higher fluorescence response due to protective and confinement effects of MOFs. It was found that H2O2 could cause much more quenching of fluorescent CuNCs/ZIF-8 than that of PEI-CuNCs, which might result from enriching H2O2 by ZIF-8. The CuNCs/ZIF-8 can be designed as a fluorescence probe to selectively and sensitively detect H2O2 with a linear range from 0.01 to 1.5µM and a LOD of 0.01µM, while those with PEI-CuNCs are 0.5-30µM and 0.50µM, respectively. Through formation of CuNCs/ZIF-8 hybrid, the sensitivity for the detection of H2O2 increases by nearly 50-fold, which makes CuNCs/ZIF-8 a desirable probe to detect H2O2 content in human serum samples. Also, we successfully demonstrated the potential application of the CuNCs/ZIF-8 for screening and evaluating activities of oxidase using glucose oxidase as a model. The glucose oxidase activity can be detected in a range of 0.1-10mU/L with a LOD of 0.1mU/L.

Impact of PD-L1, transforming growth factor-ß expression and tumor-infiltrating CD8+ T cells on clinical outcome of patients with advanced thymic epithelial tumors.

BACKGROUND: Advanced thymic epithelial tumors (TETs) are indolent and poorly responsive to chemotherapy. PD-1/PD-L1 inhibitors have shown remarkable clinical benefit in several cancers; however, many immunomodulatory molecules have been identified that affect the immune response. This study examined the progonostic roles of PD-L1, transforming growth factor-ß (TGF-ß), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) in patients with TETs. METHODS: Retrospective analysis was performed on the data of 20 patients with stage IV thymic carcinoma and 13 with stage III/IV invasive thymoma. Tissue biopsies were obtained before first-line chemotherapy was administered. Protein levels were assessed by immunohistochemistry. Objective response rate, overall survival (OS), and progression-free survival (PFS) were analyzed. RESULTS: Patients with advanced thymic carcinoma exhibited higher levels of PD-L1 and TGF-ß than patients with advanced invasive thymic carcinoma (PD-L1: 65.0% vs. 46.2%, P = 0.472; TGF-ß: 65.0% vs. 15.4%, P = 0.011). Five advanced thymic carcinoma patients with low levels of PD-L1 and TGF-ß exhibited high levels of CD8 staining. The median OS was 29.5 months patients with high TGF-ß expression versus 62.9 in patients with low TGF-ß (P = 0.052). In patients with advanced thymic carcinoma, the median PFS in the high PD-L1 expression group was 13.3 months versus 23.5 (P = 0.043) in the low PD-L1, and the median OS was 50.7 months in the high CD8 expression versus 15.1 in the CD8 low group (P = 0.154). CONCLUSIONS: Our results showed the prognostic roles of PD-L1, TGF-ß, and CD8+ TILs in patients with advanced TETs, and the potential for development of anti-PD-1/PD-L1 therapies.

Characterisation of a plancitoxin-1-like DNase II gene in Trichinella spiralis.

BACKGROUND: Deoxyribonuclease II (DNase II) is a well-known acidic endonuclease that catalyses the degradation of DNA into oligonucleotides. Only one or a few genes encoding DNase II have been observed in the genomes of many species. 125 DNase II-like protein family genes were predicted in the Trichinella spiralis (T. spiralis) genome; however, none have been confirmed. DNase II is a monomeric nuclease that contains two copies of a variant HKD motif in the N- and C-termini. Of these 125 genes, only plancitoxin-1 (1095 bp, GenBank accession no. XM_003370715.1) contains the HKD motif in its C-terminus domain. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we cloned and characterised the plancitoxin-1 gene. However, the sequences of plancitoxin-1 cloned from T. spiralis were shorter than the predicted sequences in GenBank. Intriguingly, there were two HKD motifs in the N- and C-termini in the cloned sequences. Therefore, the gene with shorter sequences was named after plancitoxin-1-like (Ts-Pt, 885 bp) and has been deposited in GenBank under accession number KF984291. The recombinant protein (rTs-Pt) was expressed in a prokaryotic expression system and purified by nickel affinity chromatography. Western blot analysis showed that rTs-Pt was recognised by serum from T. spiralis-infected mice; the anti-rTs-Pt serum recognised crude antigens but not ES antigens. The Ts-Pt gene was examined at all T. spiralis developmental stages by real-time quantitative PCR. Immunolocalisation analysis showed that Ts-Pt was distributed throughout newborn larvae (NBL), the tegument of adults (Ad) and muscle larvae (ML). As demonstrated by DNase zymography, the expressed proteins displayed cation-independent DNase activity. rTs-Pt had a narrow optimum pH range in slightly acidic conditions (pH 4 and pH 5), and its optimum temperature was 25°C, 30°C, and 37°C. CONCLUSIONS: This study indicated that Ts-Pt was classified as a somatic protein in different T. spiralis developmental stages, and demonstrated for the first time that an expressed DNase II protein from T. spiralis had nuclease activity.

Determination of landiolol, an ultra-short-acting ß1-receptor antagonist, in human plasma by liquid chromatography-tandem mass spectrometry.

A method for the determination of landiolol, an ultra-short-acting ß1-adrenoreceptor antagonist, in human plasma has been developed and validated. With the addition of pyridostigmine bromide to stabilize landiolol in the blood/plasma samples, and bisoprolol as internal standard, plasma samples were subjected to liquid-liquid extraction with diethyl ether:dicholoromethane (60:40, v/v) prior to assay by liquid chromatography-tandem mass spectrometry. Separation was performed on a TC-C18 column (150 mm × 4.6 mm, 5 µm) using a mobile phase of methanol:10 mM ammonium acetate containing 1% formic acid (65:35, v/v) in a run time of 3.5 min. Detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring of the precursor-to-product ion transitions of landiolol at m/z 510.1→157.2 and bisoprolol at m/z 326.3→116.1. The method was linear over the concentration range 0.5-500 ng/ml with a lower limit of quantitation of 0.5 ng/ml. Intra- and inter-day precisions (as relative standard deviation, RSD) were <4.4% and <10.0%, respectively, with accuracy (as relative error, RE) <10.0%. The method was successfully applied to a clinical pharmacokinetic study involving a continuous infusion of landiolol hydrochloride to healthy Chinese volunteers.

Chemiluminescence of synephrine based on the cerium(IV)-rhodamine B system.

A new chemiluminescence (CL) method is described for the determination of synephrine. It is based on the reaction between synephrine and Ce(IV) in a nitric acid medium and measurement of the CL intensity produced by rhodamine B used as a luminophore, similar to luminol or lucigenin in basic media, instead of as a sensitizer. In the optimum conditions, the increase of CL intensity was correlated with synephrine concentration over the range 5.0 x 10(-9)-1.0 x 10(-6) g/mL with a detection limit of 1.0 x 10(-9) g/mL. The relative standard deviation (RSD) was 2.9% for 1.0 x 10(-7) g/mL synephrine (n = 11). The method was applied to the determination of a drug in herbal products, citrus fruit and biological samples, with satisfactory results. The results given by the proposed method are in good agreement with those given by HPLC-UV and UV spectrophotometry.