Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD. Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2. The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3ß pathway, ameliorating tau phosphorylation. The sTREM2 (77-89) fragment, which is the minimal active sequence of sTREM2 to activate TG2, mimics the inhibitory effect of sTREM2 on tau phosphorylation. Overexpression of sTREM2 or administration of the active peptide rescues tau pathology and behavioral defects in the tau P301S transgenic mice. Together, these findings demonstrate that the sTREM2-TG2 interaction mediates the cross-talk between microglia and neurons. sTREM2 and its active peptide may be a potential therapeutic intervention for tauopathies including AD.

Dichotomy value iteration with parallel learning design towards discrete-time zero-sum games.

In this paper, a novel parallel learning framework is developed to solve zero-sum games for discrete-time nonlinear systems. Briefly, the purpose of this study is to determine a tentative function according to the prior knowledge of the value iteration (VI) algorithm. The learning process of the parallel controllers can be guided by the tentative function. That is to say, the neighborhood of the optimal cost function can be compressed within a small range via two typical exploration policies. Based on the parallel learning framework, a novel dichotomy VI algorithm is established to accelerate the learning speed. It is shown that the parallel controllers will converge to the optimal policy from contrary initial policies. Finally, two typical systems are used to demonstrate the learning performance of the constructed dichotomy VI algorithm.

Custom-made radiotherapy prosthesis for external and internal radiotherapy in a patient with lip cancer.

Definitive radiotherapy is an effective treatment for early-stage lip cancer. The goal of radiotherapy is to irradiate the cancer site effectively while protecting healthy surrounding tissue from the adverse effects of radiation. To this end, radiotherapy prostheses have been widely and effectively used. A maxillofacial prosthodontist working in collaboration with a radiation oncologist can create a custom-made radiotherapy prosthesis that minimizes adverse effects. This report demonstrates the successful use of spacers in external beam radiotherapy and brachytherapy in consideration of the patient's radiation therapy treatment plan and wearing conditions, ensuring adequate availability and preventing radiation-related complications.

The R2R3MYB transcription factors MaMYBF and MaMYB1 regulate flavonoid biosynthesis in grape hyacinth.

R2R3 MYBs play vital roles in the regulation of flavonoid biosynthesis. However, the regulatory network of R2R3 MYBs in flavonoid biosynthesis is not fully understood in grape hyacinth (Muscari spp.). Here, we identified two R2R3 MYBs, MaMYBF and MaMYB1, as potential regulators of flavonol and anthocyanin biosynthesis, respectively. MaMYBF and MaMYB1 expression was elevated during flower development and was light-induced, and the expression patterns were related to those of the flavonoid structural genes MaFLS and MaDFR, respectively. The BiFC assay verified that MaMYB1 interacts with MabHLH1, but MaMYBF does not. A dual luciferase assay revealed that MaMYBF alone strongly activated pMaFLS, and its activation was attenuated at reduced doses of MaMYBF in the presence of MabHLH1, MaMybA, and MaMYB1. MaDFR transcription mediated by MaMybA and MabHLH1 was inhibited by MaMYB1. Moreover, overexpression of MaMYBF and MaMYB1 in tobacco reduced flower pigmentation and repressed the expression of flavonoid pathway key structural genes. Therefore, MaMYBF regulates the flavonol pathway independently of cofactors. Whereas MaMYB1 regulates anthocyanin biosynthesis by binding to MabHLH1 and disrupting the MaMybA-bHLH complex in grape hyacinth. Our results offer new insights into the intricate regulatory network of flavonoids in grape hyacinth involving the regulation of both flavonol and anthocyanin.

Two B-Box Proteins, MaBBX20 and MaBBX51, Coordinate Light-Induced Anthocyanin Biosynthesis in Grape Hyacinth.

Floral colour is an important agronomic trait that influences the commercial value of ornamental plants. Anthocyanins are a class of flavonoids and confer diverse colours, and elucidating the molecular mechanisms that regulate their pigmentation could facilitate artificial manipulation of flower colour in ornamental plants. Here, we investigated the regulatory mechanism of light-induced anthocyanin biosynthesis during flower colouration in grape hyacinth (Muscari spp.). We studied the function of two B-box proteins, MaBBX20 and MaBBX51. The qPCR revealed that MaBBX20 and MaBBX51 were associated with light-induced anthocyanin biosynthesis. Both MaBBX20 and MaBBX51 are transcript factors and are specifically localised in the nucleus. Besides, overexpression of MaBBX20 in tobacco slightly increased the anthocyanin content of the petals, but reduced in MaBBX51 overexpression lines. The yeast one-hybrid assays indicated that MaBBX20 and MaBBX51 did not directly bind to the MaMybA or MaDFR promoters, but MaHY5 did. The BiFC assay revealed that MaBBX20 and MaBBX51 physically interact with MaHY5. A dual luciferase assay further confirmed that the MaBBX20-MaHY5 complex can strongly activate the MaMybA and MaDFR transcription in tobacco. Moreover, MaBBX51 hampered MaBBX20-MaHY5 complex formation and repressed MaMybA and MaDFR transcription by physically interacting with MaHY5 and MaBBX20. Overall, the results suggest that MaBBX20 positively regulates light-induced anthocyanin biosynthesis in grape hyacinth, whereas MaBBX51 is a negative regulator.

A novel R3 MYB transcriptional repressor, MaMYBx, finely regulates anthocyanin biosynthesis in grape hyacinth.

R3-MYBs negatively regulate anthocyanin pigmentation in plants. However, how R3-MYB repressors finely modulate anthocyanin biosynthesis in cooperation with R2R3-MYB activators remains unclear in monocots. We previously identified two anthocyanin-related R2R3-MYB activators (MaMybA and MaAN2) in grape hyacinth (Muscari spp.). Here, we isolated a R3-MYB repressor, MaMYBx, and characterized its role in anthocyanin biosynthesis using genetic and biochemical markers. The temporal expression pattern of MaMYBx was similar to that of MaMybA and MaAN2, and it was correlated with anthocyanin accumulation during flower development. MaMYBx could be activated either by MaMybA alone or by MaMybA/MaAN2 and cofactor MabHLH1, and it suppressed its own activation and that of MaMybA promoters mediated by MaMybA/MaAN2 and MabHLH1. Like MaMybA, MaMYBx interacted with MabHLH1. MaDFR and MaANS transcription and anthocyanin accumulation mediated by MaMybA/MaAN2 and MabHLH1 were inhibited by MaMYBx. Overexpression of MaMYBx in tobacco greatly reduced flower pigmentation and repressed the expression of late structural and regulatory anthocyanin pathway genes. Thus, MaMYBx finely regulates anthocyanin biosynthesis by binding to MabHLH1 and disrupting the R2R3 MYB-bHLH complex in grape hyacinth. The regulatory network of transcriptional activators and repressors modulating anthocyanin biosynthesis is conserved within monocots. MaMYBx seems a potentially valuable target for flower color modification in ornamental plants.

Influence of the formula on the properties of a fast dispersible fruit tablet made from mango, Chlorella, and cactus powder.

Tableting of fruit powders is gaining popularity because of the advantages it brings in, such as ease of storage, transportation, and use, and effervescent tablets could be a good alternative to accomplish fast dissolving. The present study provides a specific effervescent tablet formulation that is appropriate for the delivery of mango, cactus, and Chlorella fruit powder. The direct compression method was employed. A series of disintegration time, tensile strength, and moisture content tests were performed on the different formulations at each stage. The effects of effervescent agents' ratio, fruit powder proportion, acid and alkali content, and mannitol and lactose content on tablet properties were investigated. The results indicated that the tablet properties were highly influenced by formulation, especially the ratios of effervescent agents, fruit powders, acid to alkali ratio, as well as mannitol to lactose ratio. The best performing formulation was as follows, 45% effervescent agents (citric acid monohydrate:sodium bicarbonate = 1.3:1), 35% adhesives (mannitol:lactose = 1:8), and 20% mixed fruit powders (mango:cactus:Chlorella fruit powders = 14:5:1). With this formula, the moisture content was 3.62% and the disintegration time was 154 s, as well as a sufficient tensile strength of 2.32 MPa. Our study presented useful findings regarding the specific effects of changing ingredient ratios on tablet strength and other properties and provided a basis for the potential of using mango, cactus and microalgae powders as novel functional ingredients for fruit powder effervescent tablets. This may be used as a basis for further research on tableting.

Influence of succinylation on the conformation of yak casein micelles.

Succinylation modifies the physicochemical characteristics and improves the functional properties of proteins. This study assessed the effects of succinylation on the conformation of yak casein micelles with seven degree of modification. The results revealed that succinylation contributed to the dissociation of casein micelles. With the increase of succinylated degree, soluble nitrogen and minerals content increased, while casein micelle size and polydispersity index of micelles decreased. Succinylation affected the spatial conformation of yak casein micelles: turn decreased, ß-sheet and α-helix increased, and irregular structure were non-significantly affected. The intrinsic and ANS fluorescence intensity decreased and the maximum emission wavelength shifted red with increasing succinylation. Based on the results, the structure of yak casein micelles was characteristic of the sub-micelle model.

Clinical application of transarterial embolization for massive hemorrhage in the nasopharyngeal and maxillofacial regions.

OBJECTIVE: To study the effect and safety of transarterial embolization (TAE) in the management of massive hemorrhage in the nasopharyngeal and maxillofacial regions. METHODS: Forty-two cases of massive hemorrhage in the nasopharyngeal and maxillofacial regions were treated by TAE. Gelfoam particles, polyvinyl acohol particles, and metallic coil were used to for embolism of the external carotid artery, maxillary artery, facial artery, occipital artery, sphenopalatine artery and ascending pharyngeal artery respectively according to the angiographic findings and the region of hemorrhage sites. RESULTS: TAE was successfully performed in all the cases, and no recurrence or serious complications were observed in the 3 to 12-month follow-up. CONCLUSION: TAE is safe and effective in the treatment of massive hemorrhage in the nasopharyngeal and maxillofacial regions.