Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.

BACKGROUND: Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice. METHODS: We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or ß-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging. RESULTS: The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP). CONCLUSIONS: BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.

One Stone, Two Birds: High-Brightness Aggregation-Induced Emission Photosensitizers for Super-Resolution Imaging and Photodynamic Therapy.

Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.

Recent advances of organic emitters in deep-red light-emitting electrochemical cells.

Light-emitting electrochemical cells (LECs) are kind of easily fabricated and low-cost light-emitting devices that can efficiently convert electric power to light energy. Compared with blue and green LECs, the performance of deep-red LECs is limited by the high non-radiative rate of emitters in long-wavelength region. While various organic emitters with deep-red emission have been developed to construct high-performance LECs, including polymers, metal complexes, and organic luminous molecules (OLMs), but this is seldom summarized. Therefore, we overview the recent advances of organic emitters with emission at the deep-red region for LECs, and specifically highlight the molecular design approach and electrochemiluminescence performance. We hope that this review can act as a reference for further research in designing high-performance deep-red LECs.

Aggregation-induced emission (AIE)-active metallacycles with near-infrared emission for photodynamic therapy.

Multifunctional metallacycles with solid-state emission are highly important in cancer therapy. Here, an aggregation-induced emission (AIE)-active metallacycle of DTPABT-MC-R is developed with efficient emission in the NIR region in the solid state (PLQYs = 4.92%). DTPABT-MC-R-based nanoparticles also display excellent photo-stability, and impressive photosensitive characteristics (ROS efficiency = 10.74%), finally leading to applications in cellular imaging and photodynamic therapy (PDT).

Gait Parameters can Reflect Cognitive Performance in Older Adults with Cerebral Small Vessel Disease: A Cross-sectional Research.

BACKGROUND: Cerebral small vessel disease (CSVD) is a common chronic progressive disease. It remains unclear whether high gait variability is a marker of cognitive cortical dysfunction. METHODS: This study included 285 subjects (aged from 60 to 85 years, 60.3% female) including 37 controls, 179 presented as Fazekas II, and 69 presented as Fazekas III. The severity of white matter hyperintensities was assessed by the Fazekas Rating Scale. Gait parameters were assessed using a vision-based artificial intelligent gait analyzer. Cognitive function was tested by MMSE, MoCA, DST, and VFT. RESULTS: Three gait parameters including gait speed, gait length, and swing time were associated with cognitive performance in patients with CSVD. Gait speed was associated with cognitive performance, including MMSE (ß 0.200; 95%CI 1.706-6.018; P <.001), MoCA (ß 0.183; 95%CI 2.047-7.046; P <.001), DST (order) (ß 0.204; 95%CI 0.563-2.093; P =.001) and VFT (ß 0.162; 95%CI 0.753-4.865; P =.008). Gait length was associated with cognitive performance, including MMSE (ß 0.193; 95%CI 3.475-12.845; P =.001), MoCA (ß 0.213; 95%CI 6.098-16.942; P <.001), DST (order) (ß 0.224; 95%CI 1.056-4.839; P <.001) and VFT (ß 0.149; 95%CI 1.088- 10.114; P =.015). Swing time was associated with cognitive performance, including MMSE (ß - 0.242; 95%CI -2.639 to -0.974; P<.001), MoCA (ß -0.211; 95%CI -2.989 to -1.034; P <.001) and DST (reverse order) (ß -0.140; 95%CI -0.568 to -0.049; P =.020). CONCLUSION: This study revealed that the relationship between gait parameters and cognitive performance in patients with CSVD and the deteriorated gait parameters can reflect cognitive impairment and even dementia in older people with CSVD.

Reducing Acoustic Inhomogeneity Based on Speed of Sound Autofocus in Microwave Induced Thermoacoustic Tomography.

Microwave induced thermoacoustic tomography is a newly developing non-invasive and non-ionizing modality. In practical applications, such as breast tumor detection and brain imaging, the acoustic properties in the tissue to be detected are usually unknown and spatially non-uniform, which results in distortion and blurring of the buried targets. In this paper, a reconstruction method based on speed of sound (SoS) autofocus is proposed to reduce the effect of acoustic inhomogeneity in different soft tissues. According to this method, the number of tissue types, which are referred to as clusters in this work, can be automatically determined by a decision graph. To distinguish the boundaries of different tissues, a Gaussian Mixture Model (GMM) is fitted to the obtained image data for soft clustering instead of traditional hard clustering. Through fixing the tissue centers which are characterized by corresponding data density peaks as the means of Gaussian parameters rather than choosing them randomly, adaptive and robust reconstruction performance can be guaranteed. After performing an iterative GMM optimization, the SoS autofocus is achieved. Image reconstructed by using the updated SoS distribution is with higher accuracy than that with homogeneous assumption. Compared with the existing similar methods, the proposed method strategy obviates the need of extra experiment costs, and possesses good robustness with respect to hard assignment model errors when the medium is relatively complex. Realistic breast model and brain model simulations combined with experiments of agar phantom and pig's brain are provided to demonstrate the effectiveness of the proposed method.

LINE-1 ORF-1p enhances the transcription factor activity of pregnenolone X receptor and promotes sorafenib resistance in hepatocellular carcinoma cells.

BACKGROUND: LINE-1 ORF-1p is encoded by the human pro-oncogene LINE-1. Our previous work showed that LINE-1 ORF-1p could enhance the resistance of hepatocellular carcinoma (HCC) cells to antitumor agents. However, the mechanisms involved in LINE-1 ORF-1p-mediated drug resistance remain largely unknown. MATERIALS AND METHODS: The endogenous mRNA level of LINE-1 ORF-1p in clinical HCC specimens was examined using quantitative PCR (qPCR). The prognosis of HCC patients was assessed using time to progression and overall survival. The transcription factor activity of pregnenolone X receptor (PXR) was examined using luciferase gene reporter assays, qPCR, chromatin immunoprecipitation assays and cellular subfraction assays. Protein interaction between LINE-1 ORF-1p and PXR was detected by co-immunoprecipitation. The effect of LINE-1 ORF-1p on sorafenib resistance in HCC cells was studied using in vitro and in vivo models. RESULTS: A high level of LINE-1 ORF-1p in clinical specimens was related to poor prognosis in patients who received sorafenib treatment. LINE-1 ORF-1p increased the transcription factor activity of PXR by interacting with PXR and enhancing its cytoplasmic/nuclear translocation, and recruiting PXR to its downstream gene promoter, in turn enhancing the expression of the sorafenib resistance-related genes, CYP3A4 and mdr-1. LINE-1 ORF-1p enhanced the resistance to and clearance of sorafenib in HCC cells. CONCLUSION: LINE-1 ORF-1p enhances the transcription factor activation of PXR and promotes the clearance of and resistance to sorafenib in HCC cells.

Reducing the effects of acoustic heterogeneity with an iterative reconstruction method from experimental data in microwave induced thermoacoustic tomography.

PURPOSE: An iterative reconstruction method has been previously reported by the authors of this paper. However, the iterative reconstruction method was demonstrated by solely using the numerical simulations. It is essential to apply the iterative reconstruction method to practice conditions. The objective of this work is to validate the capability of the iterative reconstruction method for reducing the effects of acoustic heterogeneity with the experimental data in microwave induced thermoacoustic tomography. METHODS: Most existing reconstruction methods need to combine the ultrasonic measurement technology to quantitatively measure the velocity distribution of heterogeneity, which increases the system complexity. Different to existing reconstruction methods, the iterative reconstruction method combines time reversal mirror technique, fast marching method, and simultaneous algebraic reconstruction technique to iteratively estimate the velocity distribution of heterogeneous tissue by solely using the measured data. Then, the estimated velocity distribution is used subsequently to reconstruct the highly accurate image of microwave absorption distribution. Experiments that a target placed in an acoustic heterogeneous environment are performed to validate the iterative reconstruction method. RESULTS: By using the estimated velocity distribution, the target in an acoustic heterogeneous environment can be reconstructed with better shape and higher image contrast than targets that are reconstructed with a homogeneous velocity distribution. CONCLUSIONS: The distortions caused by the acoustic heterogeneity can be efficiently corrected by utilizing the velocity distribution estimated by the iterative reconstruction method. The advantage of the iterative reconstruction method over the existing correction methods is that it is successful in improving the quality of the image of microwave absorption distribution without increasing the system complexity.

Laplacian normalization and random walk on heterogeneous networks for disease-gene prioritization.

Random walk on heterogeneous networks is a recently emerging approach to effective disease gene prioritization. Laplacian normalization is a technique capable of normalizing the weight of edges in a network. We use this technique to normalize the gene matrix and the phenotype matrix before the construction of the heterogeneous network, and also use this idea to define the transition matrices of the heterogeneous network. Our method has remarkably better performance than the existing methods for recovering known gene-phenotype relationships. The Shannon information entropy of the distribution of the transition probabilities in our networks is found to be smaller than the networks constructed by the existing methods, implying that a higher number of top-ranked genes can be verified as disease genes. In fact, the most probable gene-phenotype relationships ranked within top 3 or top 5 in our gene lists can be confirmed by the OMIM database for many cases. Our algorithms have shown remarkably superior performance over the state-of-the-art algorithms for recovering gene-phenotype relationships. All Matlab codes can be available upon email request.

Evaluation of contrast enhancement by carbon nanotubes for microwave-induced thermoacoustic tomography.

Microwave-induced thermoacoustic tomography (MITAT) is a hybrid method which constructs images with ultrasound spatial resolution while exploiting dielectric contrast at microwave frequency. It has great potential in biomedical imaging especially in early breast cancer detection. The detection of early stage breast tumor in MITAT is challenged by the moderate endogenous dielectric contrast between malignant and healthy glandular tissues. In order to overcome this limitation, the performance of using carbon nanotubes (CNTs) as an imaging contrast enhancement agent is evaluated. First, the influences in dielectric and acoustic properties caused by CNTs are measured. Second, based on the measurements and the published data, numerical breast phantom is created and then used to explore the contrast enhancing effect of CNTs for MITAT, by an integrated simulation approach in both electromagnetic and acoustic field. With an experimental MITAT system, the thermoacoustic responses of tissue mimicking materials with different CNTs concentrations are also quantitatively investigated. Finally, the effectiveness of the contrast agent is also validated experimentally by using a MITAT system. The results show that the using of the dielectric contrast agent can effectively enhance the contrast of the MITAT image.

Active adjoint modeling method in microwave induced thermoacoustic tomography for breast tumor.

To improve the model-based inversion performance of microwave induced thermoacoustic tomography for breast tumor imaging, an active adjoint modeling (AAM) method is proposed. It aims to provide a more realistic breast acoustic model used for tumor inversion as the background by actively measuring and reconstructing the structural heterogeneity of human breast environment. It utilizes the reciprocity of acoustic sensors, and adapts the adjoint tomography method from seismic exploration. With the reconstructed acoustic model of breast environment, the performance of model-based inversion method such as time reversal mirror is improved significantly both in contrast and accuracy. To prove the advantage of AAM, a checkerboard pattern model and anatomical realistic breast models have been used in full wave numerical simulations.

Microwave-induced thermal acoustic tomography for breast tumor based on compressive sensing.

Microwave-induced thermal acoustic tomography (MITAT) is an innovative technique to image biomedical tissues based on their electric properties. It has the advantages of both high contrast and high spatial resolution. Image reconstruction method in MITAT is always a critical issue. In this paper, a CS-MITAT (CS: compressive sensing) imaging method is proposed. Compressive sensing (CS) is a recently developed sparse signal representation and analysis framework which handles medical imaging measurements using low sampling rate or increasing imaging quality. The CS-MITAT imaging method applies CS theory to the MITAT for breast tumor imaging. In this method, an over-complete dictionary is established to make sparse measurements in the spatial domain. This treatment greatly saves measurement time. Simulations and experiments with real breast tumor tissues demonstrate the feasibility and effectiveness of the method. Compared with conventional time reversal mirror method which has been used in MITAT research, CS-MITAT provides the same peak signal-to-noise ratio imaging quality by using significantly fewer acoustic sensor positions or scanning times.

A prototype system of microwave induced thermo-acoustic tomography for breast tumor.

Microwave-induced thermo-acoustic tomography (MITAT) is an innovative technique for tumor's detection. Due to there has high contrast in terms with permittivity and electrical conductivity of tumor versus normal tissue, even if the tumor still in the early phase it can be imaged clearly. For the proposed MITAT system, low energy microwave pulses are used as the irradiating signals, while the received signals are ultrasound, high contrast and high resolution images can be obtained. After some theoretical research and basic fundamental experiments, the first prototype of experimental system is designed and built. It includes the microwave radiator, the arrayed sensor bowl, the circular scanning platform, the system controller and the signal processor. Based on the experimental results using this integral MITAT clinic system, the images contrast can be reached higher than 383:1; while the sub-millimeter special resolution is obtained for a 1cm(3) scale tumor mimic.