Hypoxia signaling in the adipose tissue.

Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in human and rodent models of obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues behave in response to hypoxia. Then, the differential roles of adipose HIF-1α and HIF-2α in adipose tissue biology and obesity pathology are highlighted. Finally, the review emphasizes the importance of modulating adipose hypoxia as a therapeutic avenue to assist adipose tissues in functionally adapting to hypoxic conditions, ultimately promoting adipose health and improving outcomes due to obesity.

Longitudinal associations of dietary fiber and its source with 48-week weight loss maintenance, cardiometabolic risk factors and glycemic status under metformin or acarbose treatment: a secondary analysis of the March randomized trial.

AIMS: To examine longitudinal and dose-d ependent associations between dietary fiber intake and various clinical outcomes over 48 weeks of pharmacological treatment in T2DM patients. METHODS: In this secondary analysis, we used data from the MARCH trial, which was designed to compare the efficacy of acarbose or metformin monotherapy as the initial therapy in Chinese patients newly diagnosed with T2DM. Dietary data were obtained using a 24-h dietary recall method to evaluate the intakes of dietary fiber from different sources as well as the carbohydrate-to-fiber ratio. RESULTS: A total of 551 newly-diagnosed patients with T2DM complete dietary records (286 in the acarbose group and 265 in the metformin group) were included. Higher intake of total fiber and whole grain fiber was positively associated with better ß-cell function, insulin sensitivity and postprandial glycemic control under acarbose treatment. Higher intake of legume fiber was associated with better glycemic control under both acarbose and metformin treatment but with better weight loss only under metformin treatment. A high-carbohydrate-low-fiber diet was associated with worse glycemic control and lower HDL-C under acarbose treatment but with higher insulin sensitivity and better weight loss under metformin treatment. CONCLUSIONS: The notable effects of various dietary fibers when combined with different oral glucose-lowering medications should be considered to maximize therapeutic benefit.

Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications.

For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.

Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population.

BACKGROUND: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. METHODS: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. RESULTS: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10- 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (ß = -0.551, p = 6.65 × 10- 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. CONCLUSION: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. TRIAL REGISTRATION: Not applicable.

Biocompatibility and corrosion resistance of drug coatings with different polymers for magnesium alloy cardiovascular stents.

Recently, advances in enhancing corrosion properties through various techniques, and the clinical application of biodegradable cardiovascular stents made from magnesium (Mg) alloys face challenges to corrosion resistance, blood compatibility, and biocompatibility. Drug-eluting stents (DES) offer a solution to enhance the corrosion resistance of Mg alloys while simultaneously reducing the occurrence of restenosis. In this study, WE43 Mg alloy was pretreated using electropolishing technology, and different polymers (PEG and PLLA) were used as drug-polymer coatings for the Mg alloy. At the same time, PTX, an anticoagulant, was incorporated to achieve drug coating of different polymers on WE43 Mg alloy. The corrosion resistance of different polymer-drug coatings was assessed using a plasma solution. Furthermore, in vitro and in vivo tests were used to evaluate the blood biocompatibility of these coatings. The results indicated the PTX-PEG-coated WE43 Mg alloy exhibited the highest corrosion resistance and the most stable drug release profile among the tested coatings. Its hemolysis rate of 0.6 % was within the clinical requirements (<5 %). The incorporation of PEG prevents non-specific protein adsorption and nanoparticle aggregation, enhancing the surface hemocompatibility of WE43 Mg alloy. Therefore, the PTX-PEG coating shows promising potential for application in the development of drug-coated Mg alloy.

Effects of plant nutrient acquisition strategies on biomass allocation patterns in wetlands along successional sequences in the semi-arid upper Yellow River basin.

The ecological environment of wetlands in semi-arid regions has deteriorated, and vegetation succession has accelerated due to climate warming-induced aridification and human interference. The nutrient acquisition strategies and biomass allocation patterns reflect plant growth strategies in response to environmental changes. However, the impact of nutrient acquisition strategies on biomass allocation in successional vegetation remains unclear. We investigated 87 plant communities from 13 wetland sites in the semi-arid upper Yellow River basin. These communities were divided into three successional sequences: the herbaceous community (HC), the herbaceous-shrub mixed community (HSC), and the shrub community (SC). The nutrient composition of stems and leaves, as well as the biomass distribution above and belowground, were investigated. Results revealed that aboveground biomass increased with succession while belowground biomass decreased. Specifically, SC exhibited the highest stem biomass of 1,194.53 g m-2, while HC had the highest belowground biomass of 2,054.37 g m-2. Additionally, significant positive correlations were observed between leaf and stem biomasses in both HC and SC. The nitrogen (N) and phosphorus (P) contents within aboveground parts displayed an evident upward trend along the succession sequence. The highest N and P contents were found in SC, followed by HSC, and the lowest in HC. Stem N was negatively correlated with stem, leaf, and belowground biomass but positively correlated with root-shoot ratio. Leaf P displayed positive correlations with aboveground biomass while showing negative correlations with belowground biomass and root-shoot ratio. The ratios of C:N, C:P, and N:P in stem and leaf exhibited positive correlations with belowground biomass. The random forest model further demonstrated that stem N and leaf P exerted significant effects on aboveground biomass, while leaf P, stem N and P, and leaf C:P ratio had significant effects on belowground components. Additionally, the root-shoot ratio was significantly influenced by leaf P, leaf C:P ratio, and stem N, P, and C:P ratio. Therefore, the aboveground and belowground biomasses exhibited asynchronism across successional sequences, while plant nutrient acquisition strategies, involving nutrient levels and stoichiometric ratios, determined the biomass allocation pattern. This study offers valuable insights for assessing vegetation adaptability and formulating restoration plans in the semi-arid upper Yellow River basin.

Association of air pollutants with psychiatric disorders: a two-sample Mendelian randomization.

BACKGROUND: The link between air pollution and increased risk of psychiatric disorders has been growing in evidence. However, the causal relationship between air pollution and psychiatric disorders remains poorly understood. METHODS: Single-nucleotide polymorphisms associated with air pollutants (including NOx, NO2, PM2.5, PM2.5-10, and PM10) from the UK Biobank were used as instrumental variables. Summary-level data for psychiatric disorders (major depressive disorder, anxiety, bipolar disorder, schizophrenia, post-traumatic stress disorder, attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, and obsessive-compulsive disorder) were procured from the Psychiatric Genomics Consortium and FinnGen consortium. Two-sample Mendelian randomization (MR) analysis was conducted to analyze the causal associations. RESULTS: The MR analysis revealed significant associations between certain air pollutants and specific types of psychiatric disorders. The inverse-variance weighted model of preliminary analysis indicated that genetically predicted NO2 was associated with increased risks of major depressive disorder (odds ratio [OR]: 1.13, 95 % confidence intervals [CI]: 1.00-1.28, P = 0.041), bipolar disorder (OR: 1.26, 95 % CI: 1.00-1.58, P = 0.0497), schizophrenia (OR: 1.57, 95 % CI: 1.23-2.00, P < 0.001), attention deficit hyperactivity disorder (OR: 1.61, 95 % CI: 1.25-2.09, P < 0.001) and autism spectrum disorder (OR: 1.39, 95 % CI: 1.01-1.91, P = 0.044). Genetically predicted PM2.5 showed a positive association with the risk of major depressive disorder (OR: 1.21, 95 % CI: 1.06-1.39, P = 0.006), bipolar disorder (OR: 1.32, 95 % CI: 1.03-1.69, P = 0.030) and attention deficit hyperactivity disorder (OR: 1.57, 95 % CI: 1.16-2.12, P = 0.004). In addition, our results also indicated that NOx (OR: 1.64, 95 % CI: 1.21-2.21, P = 0.0012) and PM10 (OR: 1.70, 95 % CI: 1.23-2.36, P = 0.0014) could increase the risk of attention deficit hyperactivity disorder. CONCLUSIONS: The MR analysis provides evidence for the causality of different air pollutants on specific psychiatric disorders, underscoring the importance of mitigating air pollution to reduce the risk of psychiatric disorders.

Stereoselective synthetic approach toward ß-trifluoromethyl vinyl ethers and diethers via reaction of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene with phenols.

A convenient method for synthesizing ß-trifluoromethyl vinyl ethers and diethers through the base-mediated C-O coupling of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene and phenols has been developed. Remarkably, the present process shows perfect regioselective and stereoselective yield of the Z/E isomers for ß-trifluoromethyl vinyl ethers with high efficiency. Additionally, ß-trifluoromethyl vinyl diethers with identical/diverse phenoxy groups were also obtained and the regulation of the product configuration was achieved. These reactions feature transition-metal-free conditions, wide substrate scope, and atom economy.

RETNet: Resolution enhancement Transformer network for magnetic particle imaging based on X-space.

Magnetic Particle Imaging (MPI) can visualize the concentration distribution of superparamagnetic iron-oxide nanoparticles (SPIONs) in tissues with the advantages of high sensitivity and high temporal resolution. However, the low spatial resolution of MPI limits its application. Increasing the gradient strength of the selection field can improve the resolution of MPI, but also increase power consumption and noise. A feasible and cost-effective method to address this limitation is to reconstruct high gradient (HG) image from low gradient (LG) image using algorithms. Deep learning has been a powerful tool for improving the resolution of medical imaging techniques. In this study, we propose a Resolution Enhancement Transformer Network (RETNet) for reconstructing HG image with high-resolution from LG image with low-resolution as input, avoiding high power consumption and high noise in the system with HG field. RETNet leverages a shallow feature extractor to capture shallow features, a cross-scale-Transformer (CST) to focus on textural features, a residual-swin-Transformer (RST) to focus on structural features, and an image reconstruction module to aggregate these three types of features and reconstruct the HG image. Textural and structural features extracted can ensure the integrity of the details and the realization of high definition in the reconstructed image. Ablation experiments demonstrate the significant contribution of these two modules to reconstruct the HG image. Comparative experiments, including experiments at noise-free and multiple noise levels, confirm the high robustness of RETNet. Simulation, phantom, and in vivo experiments consistently demonstrate that RETNet outperforms competing methods and effectively improves the resolution of MPI.

An Analysis of Capsaicin, Dihydrocapsaicin, Vitamin C and Flavones in Different Tissues during the Development of Ornamental Pepper.

As a fruit and vegetable crop, the ornamental pepper is not just highly ornamental but also rich in nutritional value. The quality of ornamental pepper fruits is given in their contents of capsaicin, vitamin C (VC), flavonoids and total phenols. The study concentrated on the accumulation of capsaicin and dihydrocapsaicin in different tissues of 18 peppers during fruit growth and development. The results showed that the pericarp and placenta contained significantly higher levels of capsaicin than dihydrocapsaicin. Additionally, the placenta contained significantly higher levels of both capsaicin and dihydrocapsaicin compared to the pericarp. The content of capsaicin was in the range of 0-6.7915 mg·g-1, the range of dihydrocapsaicin content was 0-5.329 mg·g-1. Interestingly, we found that the pericarp is rich in VC (5.4506 mg·g-1) and the placenta is high in flavonoids (4.8203 mg·g-1) and total phenols (119.63 mg·g-1). The capsaicin is the most important component using the correlation analysis and principal component analysis. The qPCR results substantiated that the expression of genes in the placenta was significantly higher than that in the pericarp and that the expression of genes in green ripening stage was higher than that in red ripening stage. This study could be utilized to select the best ripening stages and tissues to harvest peppers according to the use of the pepper and to the needs of producers. It not only provides a reference for quality improvement and processing for consumers and market but also provides a theoretical basis for high-quality pepper breeding.

Multispectral fluorescence imaging of EGFR and PD-L1 for precision detection of oral squamous cell carcinoma: a preclinical and clinical study.

BACKGROUND: Early detection and treatment are effective methods for the management of oral squamous cell carcinoma (OSCC), which can be facilitated by the detection of tumor-specific OSCC biomarkers. The epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) are important therapeutic targets for OSCC. Multispectral fluorescence molecular imaging (FMI) can facilitate the detection of tumor multitarget expression with high sensitivity and safety. Hence, we developed Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes, in combination with multispectral FMI, to sensitively and noninvasively identify EGFR and PD-L1 expression for the detection and comprehensive treatment of OSCC. METHODS: The expression of EGFR and PD-L1 was analyzed using bioinformatics data sources and specimens. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes were developed and tested on preclinical OSCC cell line and orthotopic OSCC mouse model, fresh OSCC patients' biopsied samples, and further clinical mouthwash trials were conducted in OSCC patients. RESULTS: EGFR and PD-L1 were specifically expressed in human OSCC cell lines and tumor xenografts. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes can specifically target to the tumor sites in an in situ human OSCC mouse model with good safety. The detection sensitivity and specificity of Nimotuzumab-ICG in patients were 96.4% and 100%, and 95.2% and 88.9% for Atezolizumab-Cy5.5. CONCLUSIONS: EGFR and PD-L1 are highly expressed in OSCC, the combination of which is important for a precise prognosis of OSCC. EGFR and PD-L1 expression can be sensitively detected using the newly synthesized multispectral fluorescence imaging probes Nimotuzumab-ICG and Atezolizumab-Cy5.5, which can facilitate the sensitive and specific detection of OSCC and improve treatment outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100045738. Registered 23 April 2021, https://www.chictr.org.cn/bin/project/edit?pid=125220.

Herb-Nanoparticle Hybrid System for Improved Oral Delivery Efficiency to Alleviate Breast Cancer Lung Metastasis.

Background: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging. Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC-Orbitrap-MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated. Results: The HNS reduced particle-mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer's patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-ß1, which altered the TME in 4T1 tumor-bearing mice. Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.

Genetic Risk Loci and Familial Associations in Migraine: A Genome-Wide Association Study in the Han Chinese Population of Taiwan.

BACKGROUND AND PURPOSE: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. METHODS: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. RESULTS: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. CONCLUSIONS: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Study on the metabolic changes and regulatory mechanism of Aspergillus flavus conidia germination.

Aspergillus flavus conidia are widespread in air; they attach to food and feed crops and secrete aflatoxins, which results in serious contamination. Germination of A. flavus conidia is the most critical step in contamination of food by A. flavus. This study aims to gain an insight into A. flavus conidia through dormancy to germination to provide a theoretical basis for inhibition of A. flavus conidia germination. The morphological changes and regulation mechanism of A. flavus conidia germination at 0, 4, 8, and 12 hours were observed. Transcriptomic and metabolomic analyses showed that conidia became active from dormancy (0 hour) to the initial stage of germination (4 hours), cellular respiration and energy metabolism increased, and amino acids and lipids were synthesized rapidly. The number of differentially expressed genes and differential metabolites was highest at this stage. Besides, we found that conidia germination had selectivity for different carbon and nitrogen sources. Compared with monosaccharides, disaccharides, as the only carbon source, significantly promoted the germination of conidia. Moreover, MepA, one of genes in the ammonium transporter family was studied. The gene deletion mutant ΔMepA had a significant growth defect, and the expression of MeaA was significantly upregulated in ΔMepA compared with the wild-type, indicating that both MepA and MeaA played an important role in transporting ammonium ions.IMPORTANCEThis is the first study to use combined transcriptomic and metabolomics analyses to explore the biological changes during germination of Aspergillus flavus conidia. The biological process with the highest changes occurred in 0-4 hours at the initial stage of germination. Compared with polysaccharides, monosaccharides significantly increased the size of conidia, while significantly decreasing the germination rate of conidia. Both MeaA and MepA were involved in ammonia transport and metabolism during conidia germination.

Factors governing the dynamics of soil organic carbon and nitrogen in wetlands undergoing management changes in a semi-arid region.

Soil organic carbon and nitrogen play pivotal roles as indicators of soil quality and ecological functioning in wetlands. The escalating impact of human activities and climate change has led to a severe degradation of wetland soils, particularly in semi-arid regions. However, an understanding of the factors governing the dynamics of total soil organic carbon (TSOC) and total soil nitrogen (TSN) in semi-arid areas remains elusive, impeding a comprehensive understanding of wetland ecological functions. The present study investigated variations in TSOC and TSN content as well as vegetation and soil physicochemical properties under five different land management practices (mowed wetlands, mowed and slightly grazed wetlands, moderately grazed wetlands, heavily grazed wetlands, and natural wetlands unaffected by human interference) in the semi-arid Songnen Plain region of China. The results revealed significant decreases in TSOC and TSN content within managed wetlands compared to natural wetlands. Moreover, positive correlations were observed between pairs of SOC-TN or their storage values for SOC (TSOC)-TN (TSN). Furthermore, TSOC and TSN exhibited significant positive associations with aboveground and belowground biomass levels, stem C:N, stem C:P, soil C:P, and soil N:P. Additionally, redundancy analysis indicated that species diversity accounted for 37.4% of the variations in TSOC-TSN while belowground biomass accounted for 8.5% of the variations. Furthermore, nutrient content within stems (particularly N content and C:P) contributed to a 37.2% variation in TSOC and TSN whereas root nutrient content (especially N:P, C:N, and C:P) contributed to a 15.3% variation. Soil C:P, C:N, and total phosphorous (TP) content accounted for 65.7%, 9.6%, and 7.5% of variations of TSOC and TSN, respectively. Besides, variation partitioning analysis revealed that plant community characteristics, community nutrient content, and soil physicochemical properties collectively influenced the dynamics of TSOC and TSN. Among these factors, soil physicochemical properties emerged as the primary drivers of carbon and nitrogen dynamics in degraded wetlands in semi-arid regions. The impact on TSN was more pronounced than that of TSOC. This study provides valuable insights for understanding the processes and mechanisms underlying carbon and nitrogen accumulation in degraded wetlands, facilitating the development of regionally adaptive management plans under different management practices.

A Novel Hand-held Multi-color Magnetic Particle Imaging Device based on Rapid Frequency Conversion.

OBJECTIVE: Multi-color Magnetic Particle Imaging (MPI) technology offers high sensitivity and non-invasive imaging capabilities. It can simultaneously image multiple superparamagnetic iron oxide nanoparticles (SPIOs), facilitating more precise detection of multiple molecular markers in vivo. However, the fixed drive frequency of existing hand-held MPI devices makes it difficult to fully match the nonlinear magnetic response of different SPIOs, affecting the spatial resolution and quantitative accuracy of multi-color imaging. METHODS: We designed a novel rapid frequency conversion based hand-held multi-color magnetic particle imaging (RFC-MPI) device. This device adjusts the drive frequency based on the nonlinear magnetic response of SPIOs at different frequencies, effectively expanding the system matrix information and thereby improving spatial resolution and multi-color imaging capabilities simultaneously. RESULTS: The device achieved a spatial resolution of 2 mm and an imaging speed of 1 frame/s. The scanning depth is 8 mm. It was used to scan a 22 cm x 22 cm area of a human-shaped phantom, verifying its potential for scanning humans. The ability of the device to identify and quantify SPIOs was validated using mice breast tumors. The quantitative accuracy during simultaneous imaging was determined to be 96.58%. CONCLUSION: Due to its innovative structural design and rapid frequency conversion method, the RFC-MPI device exhibits excellent in vivo imaging performance. Both simulation and phantom experiments have verified the effectiveness of the proposed method. SIGNIFICANCE: The hand-held RFC-MPI device can effectively improve the spatial resolution and quantitative accuracy of multi-color MPI, laying the foundation for future clinical applications.

Protocol for Seahorse analysis of ex vivo mouse brown and white adipose tissues.

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.

Dual-channel end-to-end network with prior knowledge embedding for improving spatial resolution of magnetic particle imaging.

Magnetic particle imaging (MPI) is an emerging non-invasive medical imaging tomography technology based on magnetic particles, with excellent imaging depth penetration, high sensitivity and contrast. Spatial resolution and signal-to-noise ratio (SNR) are key performance metrics for evaluating MPI, which are directly influenced by the gradient of the selection field (SF). Increasing the SF gradient can improve the spatial resolution of MPI, but will lead to a decrease in SNR. Deep learning (DL) methods may enable obtaining high-resolution images from low-resolution images to improve the MPI resolution under low gradient conditions. However, existing DL methods overlook the physical procedures contributing to the blurring of MPI images, resulting in low interpretability and hindering breakthroughs in resolution. To address this issue, we propose a dual-channel end-to-end network with prior knowledge embedding for MPI (DENPK-MPI) to effectively establish a latent mapping between low-gradient and high-gradient images, thus improving MPI resolution without compromising SNR. By seamlessly integrating MPI PSF with DL paradigm, DENPK-MPI leads to a significant improvement in spatial resolution performance. Simulation, phantom, and in vivo MPI experiments have collectively confirmed that our method can improve the resolution of low-gradient MPI images without sacrificing SNR, resulting in a decrease in full width at half maximum by 14.8%-23.8 %, and the accuracy of image reconstruction is 18.2 %-27.3 % higher than other DL methods. In conclusion, we propose a DL method that incorporates MPI prior knowledge, which can improve the spatial resolution of MPI without compromising SNR and possess improved biomedical application.

Resveratrol and (-)-Epigallocatechin-3-gallate Regulate Lipid Metabolism by Activating the AMPK Pathway in Hepatocytes.

The purpose of this study was to explore the effects of Res and EGCG on cell growth, cellular antioxidant levels, and cellular lipid metabolism in hepatocytes. In this experiment, leghorn male hepatoma (LMH) cells were used as hepatocytes. The results showed that 6.25-25 µM Res and EGCG had no adverse effects on cell viability and growth. Meanwhile, with the increasing dosage of Res and EGCG, the contents of total cholesterol (TC), total glyceride (TG), and malondialdehyde (MDA) in hepatocytes decreased significantly (p < 0.05), while the contents of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT) increased significantly (p < 0.05). In addition, western blot results showed that Res and EGCG could significantly increase the expression of p-AMPK protein and reduce the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) protein in hepatocytes (p < 0.05). Moreover, q-PCR results showed that with the increase in Res and EGCG, the expression of cholesterol- and fatty acid synthesis-related genes decreased significantly (p < 0.05). In conclusion, Res and EGCG can increase the antioxidant capacity of hepatocytes and reduce the synthesis of TC and TG in hepatocytes by activating AMPK, thereby regulating lipid metabolism in hepatocytes.