Kallistatin leads to cognition impairment via downregulating glutamine synthetase.

In many neurodegenerative disorders, such as Alzheimer's disease (AD), glutamate-mediated neuronal excitotoxicity is considered the basis for cognitive impairment. The mRNA and protein expression of SERPINA4(Kallistatin) are higher in patients with AD. However, whether Kallistatin plays a regulatory role in glutamate-glutamine cycle homeostasis remains unclear. In this study, we identified impaired cognitive function in Kallistatin transgenic (KAL-TG) mice. Baseline glutamate levels were elevated and miniature excitatory postsynaptic current (mEPSC) frequency was increased in the hippocampus, suggesting the impairment of glutamate homeostasis in KAL-TG mice. Mechanistically, we demonstrated that Kallistatin promoted lysine acetylation and ubiquitination of glutamine synthetase (GS) and facilitated its degradation via the proteasome pathway, thereby downregulating GS. Fenofibrate improved cognitive memory in KAL-TG mice by downregulating serum Kallistatin. Collectively, our study findings provide insights the mechanism by which Kallistatin regulates cognitive impairment, and suggest the potential of fenofibrate to prevente and treat of AD patients with high levels of Kallistatin.

Preparation, physicochemical and biological evaluation of chitosan Pleurotus ostreatus polysaccharides active films for food packaging.

The aim of this study was to create CS-POP composite films by blending Pleurotus ostreatus stalk polysaccharides (POP) and chitosan (CS). The effects of adding different concentrations (0 %, 0.25 %, 0.5 %, 0.75 %, and 1 %) of POP on the mechanical, barrier, and optical properties of the CS films were investigated. When the POP content is at 0.5 %, the tensile strength of the composite film reaches its maximum value at 13.691 MPa, showing a significant improvement compared to the tensile strength of the pure CS film. The structure of the CS and CS-POP composite films was characterized by FT-IR spectroscopy, XRD, TGA and SEM. The results indicate that due to the interaction between the two types of CS and POP, the formation of Schiff base, and the intermolecular hydrogen bonds between CS and POP, the addition of POP to CS films can result in a smoother and more stable crystalline structure in the composite film. The CS-POP composite films exhibited enhanced antioxidant and antibacterial activity compared to the CS films alone, with the highest DPPH scavenging activity of 72.43 %. The composite films also showed significant inhibitory effects on the growth of E. coli.

Pigment Epithelium-Derived Factor, a Novel Adipokine, Contributes to Gestational Diabetes Mellitus.

CONTEXT: Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. OBJECTIVE: This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. METHODS: In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. RESULTS: Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. CONCLUSION: In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.

Chitosan-Based Materials: An Overview of Potential Applications in Food Packaging.

Chitosan is a multifunctional biopolymer that is widely used in the food and medical fields because of its good antibacterial, antioxidant, and enzyme inhibiting activity and its degradability. The biological activity of chitosan as a new food preservation material has gradually become a hot research topic. This paper reviews recent research on the bioactive mechanism of chitosan and introduces strategies for modifying and applying chitosan for food preservation and different preservation techniques to explore the potential application value of active chitosan-based food packaging. Finally, issues and perspectives on the role of chitosan in enhancing the freshness of food products are presented to provide a theoretical basis and scientific reference for subsequent research.

Structural Biology of Nanobodies against the Spike Protein of SARS-CoV-2.

Nanobodies are 130 amino acid single-domain antibodies (VHH) derived from the unique heavy-chain-only subclass of Camelid immunogloblins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. The first nanobody agent has now entered the clinic as a treatment against a blood disorder. The spread of the SARS-CoV-2 virus has seen the global scientific endeavour work to accelerate the development of technologies to try to defeat a pandemic that has now killed over four million people. In a remarkably short period of time, multiple studies have reported nanobodies directed against the viral Spike protein. Several agents have been tested in culture and demonstrate potent neutralisation of the virus or pseudovirus. A few agents have completed animal trials with very encouraging results showing their potential for treating infection. Here, we discuss the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2.

Application of Telemedicine for Preliminary Screening of Autism Spectrum Disorder.

OBJECTIVE: Preliminary screening for autism spectrum disorder (ASD) is mainly performed offline in China. This method is time consuming, labor intensive, inefficient and costly. These complications limit its routine implementation in some hospitals and child health institutions, especially community health service centers. Thus, the present study explored the clinical applicability of an online screening system for ASD detection based on telemedicine technology. METHODS: The online screening system designed based on the WeChat platform and section A of the Chinese-validated version of the checklist for autism in toddlers (CHAT-23-A) and combined with an independent Research and Development (R&D) program. The sensitivity and specificity were 0.92 and 0.90, respectively, and the area under the receiver operating characteristic curve (AUC) values for all 23 items and 7 key items were 0.934 and 0.91, respectively. RESULTS: The online screening system based on telemedicine technology was not limited by time, space, region, or medical resources and showed high sensitivity, specificity, and diagnostic efficiency for ASD. CONCLUSION: The online screening system based on telemedicine technology is suitable for large-scale population ASD screening in childcare institutions.

Combining of transcriptome and metabolome analyses for understanding the utilization and metabolic pathways of Xylo-oligosaccharide in Bifidobacterium adolescentis ATCC 15703.

A combination of transcriptome and metabolome analyses was applied to understand the utilization and metabolism of Xylo-oligosaccharide (XOS) in Bifidobacterium adolescentis 15703 as well as identifying the key regulatory-related genes and metabolites. Samples of cultures grown on either XOS or xylose were collected. The transcript and metabolite profiles were obtained from high-throughput RNA-sequencing data analysis and UHPLC system. Compared with xylose, XOS highly promoted the growth of B. adolescentis 15703 and resulted in a growth yield about 1.5-fold greater than xylose. The transcriptome analysis showed that XOS could enhance genes, including ABC transporters, galactosidase, xylosidase, glucosidase, and amylase, which were involved in transport and metabolism of carbohydrate compared with xylose. Furthermore, the expression profile of 16 candidate genes using qRT-PCR has validated the accuracy of the RNA-seq data. Also, the metabolomic analyses, particularly those related to metabolic biomarkers of fatty acids, amino acids, and sugars showed a similar trend of result and approved the advantages of XOS as growth medium for B. adolescentis 15703 compared with xylose. The expression and abundance of specific genes and metabolites highlighted the complex regulatory mechanisms involved in utilization of XOS by B. adolescentis 15703. These results are useful in the understanding of the metabolic pathway of XOS in B. adolescentis 15703 and contribute to the optimization of XOS probiotic effects as a food additive.