Extracellular vesicles-based point-of-care testing for the diagnosis and monitoring of Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/µL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aß EVs at different time courses, and compared them with intraneuronal Aß cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer's and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.

A complex system health state assessment method with reference value optimization for interpretable BRB.

Health condition assessment is the basis for formulating and optimizing maintenance strategies of complex systems, which is crucial for ensuring the safe and stable operation of these systems. In complex system health condition assessment, it is not only necessary for the model to handle various uncertainties to ensure the accuracy of assessment results, but also to have a transparent and reasonable assessment process and interpretable, traceable assessment results. belief rule base (BRB) has been widely used as an interpretable modeling method in health condition assessment. However, BRB-based models currently face two issues: (1) inaccuracies in expert-provided parameters that can affect the model's accuracy, and (2) after model optimization, interpretability may be reduced. Therefore, this paper proposes a new method for complex system health condition assessment called interpretable BRB with reference value optimization (I-BRB). Firstly, to address the issue of inaccurate reference values, a reference value optimization algorithm with interpretability constraints is designed, which optimizes the reference values without compromising expert knowledge. Secondly, the remaining parameters are optimized using the projection covariance matrix adaptation evolution strategy (P-CMA-ES) with interpretability constraints to improve the model's accuracy. Finally, a case study evaluating the bearing components of a flywheel system is conducted to validate the proposed method. Experimental results demonstrate that I-BRB achieves higher accuracy in health condition assessment.

Space Charge Dynamics in Epoxy Resins Under the Influence of a Long-Term High Electric Field at Various Temperatures.

As the main insulating material of an ultra-high voltage (UHV) resin impregnated paper (RIP) bushing, epoxy resin accumulates space charge under the DC voltage, which would affect the insulation properties of the bushing. In this article, the evolution of space charge accumulation and dissipation within the epoxy resin samples was measured under the influence of a long-term (24 h) electric field of 60 kV/mm at 40°, 60°, 80°, and 100°C. The experimental results show that the space charge transport in the epoxy sample was a long-time dynamic process. When the temperature was not greater than 60°C, only homocharge accumulation was observed within the samples, and the space charge distribution did not reach a stable state even after 24 h of voltage application. When the temperature was not lower than 80°C, the positive heterocharge accumulation was observed at the interface between cathode and epoxy. Through analysis by fitting and numerical simulation, it was verified that the positive heterocharge accumulation was caused by the limitation of the hole extraction, and the transport of holes within the samples obeyed the jump conductance model.

Three-Dimensional MXenes for Supercapacitors: A Review.

Supercapacitors have the characteristics of high power density and long cycle life, but the low energy density limits their further development. The 2D transitional metal carbides/nitrides (MXenes) show great application prospects in the field of supercapacitors due to their superior volumetric capacitance, metallic-like conductivity, tunable surface terminations, and structural advantages. However, like other 2D materials, MXenes suffer from the inevitable problem of nanosheet restacking and aggregation, which reduces the overall active surface sites and blocks the accessibility of the electrolyte ions. The transformation of 2D MXene nanosheets into 3D architectures is proven effective to overcome the restacking problem. The review briefly summarizes the preparation strategies of 3D MXene materials, including template-assisted method, framework-assisted method, chemical assembly method, foaming method, and other methods with the discussion centered on the performances of 3D MXenes in supercapacitors. Finally, an outlook on the current progress and opportunities is given to highlight the increasing popularity of 3D MXenes in supercapacitors.

Development and evaluation of poly adenosine 5'-diphosphate-ribose polymerase 1 immobilization-based receptor chromatography.

Yanghe decoction is a traditional Chinese medicine prescription and has been used for breast cancer treatment for many years. However, the effective ingredients in the decoction have not been identified. The expression of poly(ADP-ribose) polymerase-1 is highly related to breast cancer. Using poly(ADP-ribose) polymerase-1 as a probe, we expressed the haloalkane dehalogenase-tagged protein in BL21(DE3) E. coli, immobilized it on hexachlorocaproic acid-modified macroporous silica gel, and established a poly(ADP-ribose) polymerase-1 chromatographic model. The feasibility of the model was verified by testing the retention behaviors of five drugs on the protein column. We applied the model in screening the bioactive components in yanghe decoction. Rutin, liquiritin, and a compound ([M-H]- 681.7) were identified to be the potential bioactive ingredients. We studied the binding property between rutin and poly(ADP-ribose) polymerase-1 by injection amount dependent method, competitive studies, and molecular docking. We found that rutin can bind to the protein through the typical inhibitor binding site of the protein. Therefore, the chromatographic model is a useful tool to screen bioactive compounds from traditional Chinese medicine. The method is fast, reliable, and applicable to other functional proteins that can screen the potential lead compounds for the treatment of the related diseases.

Yin-yang effect of tumour cells in breast cancer: from mechanism of crosstalk between tumour-associated macrophages and cancer-associated adipocytes.

Currently, adipocytes and macrophages are considered to be key cell types of breast cancer (BC) tissues. With the emergence of crown-like structures (CLS), cancer-associated adipocytes (CAAs) and tumour-associated macrophages (TAMs) are formed respectively in tumor microenvironment (TME). Both of them affect the progress of breast cancer, while forming crosstalk in the tumour tissue. CAAs play an important role, which produces hypoxia and inflammation environment and aggravates this environment. The formation and secretion of TAMs with M2 phenotypic characteristics, such as HIF-1α, and TNF-α, affect the progress of cancer cells by interfering with the secretion of MCP-1 by CAAs. Therefore, the interaction between CAAs and TAMs may be an effective therapeutic target for breast cancer. In this review, we focus on the biological effects of two types of cells in breast cancer, in order to better explain the crosstalk between them and provide new ideas for the future treatment of breast cancer.

Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

microRNA regulation of skin pigmentation in fish.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in numerous biological processes. However, the role of miRNAs in skin color determination in fish has not been completely determined. Here, we identified that 13 miRNAs are differentially expressed between red and white skin. The analysis of miRNA spatial and temporal expression patterns suggests that miR-429 is a potential regulator of skin pigmentation. miR-429 silencing results in an obvious change in skin pigmentation. Bioinformatics analysis and a luciferase reporter assay show that miR-429 directly regulates expression of Foxd3 by targeting its 3'-untranslated (3'-UTR) region. miR-429 silencing leads to a substantial increase in the expression of Foxd3 in vivo, thereby repressing the transcription of MITF and its downstream genes, such as TYR, TYRP1 or TYRP2. These findings would provide a novel insight into the determination of skin color in fish.

[Influence of incubation time on metabolites in mycelia of Paecilomyces militaris].

OBJECTIVE: To determine the secondary metabolites production in mycelia of Paecilomyces militaris. METHODS: Mycelia were cultured in plates with sabouraud dextrose agar yeast medium at 25 degrees C for 9 days. Sampling was done every day from the second to the ninth day. The secondary metabolites in the mycelia of Paecilomyces militaris were extracted with either methanol or ethyl acetate. The extracts were blended and analyzed by liquid chromatography-mass spectrometry (LC-MS). LC-MS data were collected and analyzed by MetaboAnalyst software. RESULT: Principal component analysis indicates different secondary metabolites accumulation with incubation times. Hierarchical clustering analysis shows that the metabolic process of cationic compounds such as alkaloids, peptides and nucleosides can be divided into three stages, and that the metabolic process of anionic compounds such as organic acids and saccharides can be divided into two stages. Metabolites difference and heat map analysis show that: (1) The number of metabolites with significant increased contents was raised significantly in mycelia of Paecilomyces militaris on the second and third incubation days. The main species with increased contents were esters and their hydrolized products, destruxin B, variotin and some unidentified nitrogin contained compounds. (2) The number of metabolites with significant raised contents was decreased significantly on the fourth and fifth incubation days. The main species with increased contents were ophiocordin and destruxin A. (3) Apart from peptide antibiotics such as several beauverolides, the content increased metabolites included also several organic acids, amino acids, rhamnose, trehalose, cerebroside and riboflavine during the sixth to ninth incubation days. CONCLUSION: The secondary metabolites in mycelia of Paecilomyces militaris were related significantly to the incubation time.

[Influence of liquid or solid culture conditions on the volatile components of mycelia of Isariacateinannulata].

OBJECTIVE: To determine the volatile components of mycelia of Isaria cateinannulata cultured under different culture conditions, and to analyze the relationships between the culture conditions and volatile metabolites. METHODS: Mycelia were cultured in solid plates with SDAY medium and liquid shake flasks with SDY medium. The culture conditions were at 25 degrees C and 8 days. Volatile components in the mycelia of I. cateinannulata were extracted with simultaneous distillation extraction and analyzed by gas chromatography-mass spectrometry. RESULT: Alkenes, alkanes, heterocyclic and polycyclic aromatic hydrocarbons (PAH) were existed abundantly both in the mycelia of liquid and solid cultures, but the kinds and relative concentrations of the volatile components in mycelia of liquid and solid cultures were very different. Forty-one compounds were identified from the mycelia of solid culture and 32 compounds were identified from the mycelia of liquid culture. Esters, quinones and oximes were only found in solid cultured mycelia whereas carboxylic acids were only discovered in the mycelia of liquid culture. At the same time, mycelia of liquid culture contained much more phenols. The most abundant compounds in mycelia of liquid and solid cultures were hydrocarbons. The volatile extracts of solid cultured mycelia contained 57.6% alkenes and 9.19% alkanes. The volatile extracts of liquid cultured mycelia contained 7.85% alkenes and 22.4% alkanes. CONCLUSION: Liquid or solid culture conditions influenced the volatile components of mycelia of I. cateinannulata.