Yes-associated protein regulates glutamate homeostasis through promoting the expression of excitatory amino acid transporter-2 in astrocytes via ß-catenin signaling.

The homeostasis of glutamate is mainly regulated by the excitatory amino acid transporters (EAATs), especially by EAAT2 in astrocytes. Excessive glutamate in the synaptic cleft caused by dysfunction or dysregulation of EAAT2 can lead to excitotoxicity, neuronal death and cognitive dysfunction. However, it remains unclear about the detailed regulation mechanism of expression and function of astrocytic EAAT2. In this study, first, we found increased neuronal death and impairment of cognitive function in YAPGFAP -CKO mice (conditionally knock out Yes-associated protein [YAP] in astrocytes), and identified EAAT2 as a downstream target of YAP through RNA sequencing. Second, the expression of EAAT2 was decreased in cultured YAP-/- astrocytes and the hippocampus of YAPGFAP -CKO mice, and glutamate uptake was reduced in YAP-/- astrocytes, but increased in YAP-upregulated astrocytes. Third, further investigation of the mechanism showed that the mRNA and protein levels of ß-catenin were decreased in YAP-/- astrocytes and increased in YAP-upregulated astrocytes. Wnt3a activated YAP signaling and up-regulated EAAT2 through ß-catenin. Furthermore, over-expression or activation of ß-catenin partially restored the downregulation of EAAT2, the impairment of glutamate uptake, neuronal death and cognitive decline that caused by YAP deletion. Finally, activation of EAAT2 also rescued neuronal death and cognitive decline in YAPGFAP -CKO mice. Taken together, our study identifies an unrecognized role of YAP signaling in the regulation of glutamate homeostasis through the ß-catenin/EAAT2 pathway in astrocytes, which may provide novel insights into the pathogenesis of brain diseases that closely related to the dysfunction or dysregulation of EAAT2, and promote the development of clinical strategy.

Chemiluminescence-Induced Free Radical-Promoted Cationic Polymerization.

Chemiluminescence (CL) has recently been featured as a new external light source for various photoinduced reactions with attractive features such as eliminating continuous energy supply and advanced light source setups. In the present study, the free-radical-promoted cationic polymerization of cyclohexene oxide, n-butyl vinyl ether, and N-vinyl carbazole under CL irradiation is described. The method is based on the visible-light-induced generation of electron donor radicals from bis-(4-methoxybenzoyl)diethyl germane (BAG), bis(2,4,6-trimethylbenzoyl) phenyl phosphinate, and camphorquinone by CL illumination followed by electron transfer to diphenyl iodonium hexafluorophosphate (Ph2 I+ PF6 - ) to form corresponding cations capable of initiating cationic polymerization. The applicability of the process to network formation is also demonstrated by using a bifunctional monomer, tri(ethylene glycol) divinyl ether.

Near-Infrared-Induced Cationic Polymerization Initiated by Using Upconverting Nanoparticles and Titanocene.

A new near-infrared (NIR)-sensitized photoinitiating system for free-radical-promoted cationic polymerization of oxirane and vinyl monomers such as cyclohexene oxide, and n-butyl vinyl ether (BVE), and N-vinyl carbazole (NVC) is described. A three-component photoinitiating system consists of upconverting nanoparticles (UCNPs), titanium-complex free radical photoinitiator (Irgacure 784, titanocene), and diphenyl iodonium hexafluorophosphate (Ph2 I+ PF6 - ). Upon NIR laser irradiation at 980 nm, the radicals generated from titanocene by the visible light emitted by UCNP abstract hydrogen or add to the monomer, forming electron donor radicals that can be oxidized by iodonium salt to initiate cationic polymerization.

Optimization of Extended-Release ZL-004 Nanosuspensions for In Vivo Pharmacokinetic Study to Enhance Low Solubility and Compliance.

ZL-004, a promising small molecule that increases white blood cell counts, was developed for extended-release nanosuspensions to improve low solubility and compliance of patients. In vivo pharmacokinetic studies of nanosuspensions with different particle sizes and administration volumes were conducted. Unexpectedly, Cmax of NS-PC-L (1156 nm) was 1.3 fold higher than NS-PB-L (836 nm), and area under plasma concentration-time curve (AUC) was similar. It suggested that in vivo behavior of nanosuspensions was influenced significantly by the original dissolved drug, which did not only rely on the particle size but also the amount of the free stabilizers. In addition, smaller administration volume (0.1 mL) achieved significantly lower Cmax and AUC than the higher volume (0.5 mL), due to the reduced amount of dissolved drug. DSC and XPRD demonstrated that the crystal forms of nanosuspensions prepared by the precipitation method and high-pressure homogenization were similar; therefore, in vivo behaviors did not show significant differences. An additional 0.15% PEG 4000 enhanced the redispersity and maintained the particle size for 3 months. Finally, a nanosuspensions with the desired initial release was achieved, which lasted approximately 32 days steadily after a single dose. AUC and t1/2 were 161.2 fold and 22.9 fold higher than oral administration.

Fabrication and functional application of zein-based core-shell structures: A review.

Core-shell structures exhibit a number of distinct absorptive properties that make them attractive tools for use in a range of industrial contexts including pharmaceuticals, biotechnology, cosmetics, and food/agriculture. Several recent studies have focused on the development and fabrication of zein-based core-shell structures for a range of functional material deliveries. However, no recent review article has evaluated the fabrication of such core-shell structures for food-based applications. In this paper, we therefore survey current approaches to fabricating different zein-based platforms including particles, fibers, films, and hydrogels that have appeared in a variety of functionally relevant applications. In addition, we highlight certain challenges and future research directions in this field, thereby providing a novel perspective on zein-based core-shell structures.

Liquid-liquid biopolymers aqueous solution segregative phase separation in food: From fundamentals to applications-A review.

As a result of the spontaneous movement of molecules, liquid-liquid biopolymer segregative phase separation takes place in an aqueous solution. The efficacy of this type of separation can be optimized under conditions where variables such as pH, temperature, and molecular concentrations have minimal impact on its dynamics. Recently, interest in the applications of biopolymers and their segregative phase separation-associated molecular stratification has increased, particularly in the food industry, where these methods permit the purification of specific particles and the embedding of microcapsules. The present review offers a comprehensive examination of the theoretical mechanisms that regulate the liquid-liquid biopolymers aqueous solution segregative phase separation, the factors that may exert an impact on this procedure, and the importance of this particular separation method in the context of food science. These discussion points also address existing difficulties and future possibilities related to the use of segregative phase separation in food applications. This highlights the potential for the design of novel functional foods and the enhancement of food properties.

Formation, influencing factors, and applications of internal channels in starch: A review.

Starch, a natural polymer, has a complex internal structure. Some starches, such as corn and wheat starches, have well-developed surface pores and internal channels. These channel structures are considered crucial in connecting surface stomata and internal cavities and have adequate space for loading guest molecules. After processing or modification, the starch-containing channel structures can be used for food and drug encapsulation and delivery. This article reviews the formation and determination of starch internal channels, and the influence of different factors (such as starch species and processing conditions) on the channel structure. It also discusses relevant starch preparation methods (physical, chemical, enzymatic, and synergistic), and the encapsulation effect of starch containing internal channels on different substances. In addition, the role of internal channels in regulating the starch digestion rate and other aspects is also discussed here. This review highlights the significant multifunctional applications of starch with a channel structure.

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease.

Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aß deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aß deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.

3D printing of unsupported multi-scale and large-span ceramic via near-infrared assisted direct ink writing.

In the three-dimensional printing process of ceramic with low-angle structures, additional supporting structures are usually employed to avoid collapse of overhanging parts. However, the extra supporting structures not only affect printing efficiency, but the problems caused by their removal are also a matter of concern. Herein, we present a ceramic printing method, which can realize printing of unsupported multi-scale and large-span ceramics through the combination of direct ink writing and near-infrared induced up-conversion particles-assisted photopolymerization. This printing technology enables in-situ curing of multi-scale filaments with diameters ranging from 410 µm to 3.50 mm, and ceramic structures of torsion spring, three-dimensional bending and cantilever beam were successfully constructed through unsupported printing. This method will bring more innovation to the unsupported 3D manufacturing of complex shape ceramics.

A COMPARISON STUDY ON INFANT-PARENT VOICE DIARIZATION.

We design a framework for studying prelinguistic child voice from 3 to 24 months based on state-of-the-art algorithms in diarization. Our system consists of a time-invariant feature extractor, a context-dependent embedding generator, and a classifier. We study the effect of swapping out different components of the system, as well as changing loss function, to find the best performance. We also present a multiple-instance learning technique that allows us to pre-train our parameters on larger datasets with coarser segment boundary labels. We found that our best system achieved 43.8% DER on test dataset, compared to 55.4% DER achieved by LENA software. We also found that using convolutional feature extractor instead of logmel features significantly increases the performance of neural diarization.

3D printing of multi-scalable structures via high penetration near-infrared photopolymerization.

3D printing consisted of in-situ UV-curing module can build complex 3D structures, in which direct ink writing can handle versatile materials. However, UV-based direct ink writing (DIW) is facing a trade-off between required curing intensity and effectiveness range, and it cannot implement multiscale parallelization at ease. We overcome these difficulties by ink design and introducing near-infrared (NIR) laser assisted module, and this increases the scalability of direct ink writing to solidify the deposited filament with diameter up to 4 mm, which is much beyond any of existing UV-assisted DIW. The NIR effectiveness range can expand to tens of centimeters and deliver the embedded writing capability. We also demonstrate its parallel manufacturing capability for simultaneous curing of multi-color filaments and freestanding objects. The strategy owns further advantages to be integrated with other types of ink-based 3D printing technologies for extensive applications.

Photopolymerization of Macroscale Black 3D Objects Using Near-Infrared Photochemistry.

The efficiency of the photopolymerization technology significantly decreases when the color of materials blackens, which is contributed by the limitations of light penetration. Herein, we demonstrate rapid generation of black 3D objects up to the centimeter level in size based on melanin using near-infrared (NIR) photochemistry. Melanin, of a low absorption coefficient in the NIR range, allows thorough penetration of the 980 nm light to induce emission from upconversion nanoparticles (UCNPs) for initiating UCNP-assisted photopolymerization (UCAP). A model that describes light-attenuation gradients and dose-dependent kinetics in UCAP-guided NIR photochemistry is developed. Notably, the established model for the UCAP concept provides sufficient vertical light penetration to form scale-predictable black materials and instructs 3D printing applications. The critical control parameters were evaluated, and it was shown that complex macroscale black objects can be processed within dozens of minutes. The modeling methodologies integrated with rich functional fillers will further extend the versatility of UCAP technology in device design and manufacturing.