Metabonomic Profiles Delineate the Effect of Traditional Chinese Medicine Sini Decoction on Myocardial Infarction in Rats

Background: In spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI), it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM) uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body’s normal function can be restored. Sini decoction (SND) is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components. Methodology/Principal Findings: A urinary metabonomic method based on nuclear magnetic resonance and ultra highperformance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism. Conclusions/Significance: Our results showed that metabonomic approach offers a useful tool to identify MI-relate

Potential Biomarkers in Mouse Myocardium of Doxorubicin-Induced Cardiomyopathy: A Metabonomic Method and Its Application

BACKGROUND: Doxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is limited because of the risk of severe cardiotoxicity. Though numerous studies have ascribed DOX cardiomyopathy to specific cellular pathways, the precise mechanism remains obscure. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against DOX-induced cardiomyopathy. However, its action mechanisms are not well known due to its complex components. METHODOLOGY/PRINCIPAL FINDINGS: A tissue-targeted metabonomic method using gas chromatography-mass spectrometry was developed to characterize the metabolic profile of DOX-induced cardiomyopathy in mice. With Elastic Net for classification and selection of biomarkers, twenty-four metabolites corresponding to DOX-induced cardiomyopathy were screened out, primarily involving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of TCM SND, which showed that SND administration could provide satisfactory effect on DOX-induced cardiomyopathy through partially regulating the perturbed metabolic pathways. CONCLUSIONS/SIGNIFICANCE: The results of the present study not only gave rise to a systematic view of the development of DOX-induced cardiomyopathy but also provided the theoretical basis to prevent or modify expected damage

Systems-Level Immunomonitoring from Acute to Recovery Phase of Severe COVID-19

Peer reviewe

Synchronous post-acceleration of laser-driven protons in helical coil targets by controlling the current dispersion

Post-acceleration of protons in helical coil targets driven by intense, ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’ self-discharge. The acceleration length of protons can exceed a few millimeters, and the acceleration gradient is of the order of GeV/m. How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration. In this paper, we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons. We propose a scheme using a two-stage helical coil to control the current dispersion. With optimized parameters, the energy gain of protons is increased by four times. Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser, or more than 100 MeV using a petawatt laser, by controlling the current dispersion

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Multiomic analysis of T cells in response to cancers and microbes

The human immune system consists of various cell subsets, cytokines and their interactions. Traditionally researchers focus on one compartment at a time, however, with the advance in high-throughput, multi-omics techniques, it is possible to monitor multiple compartments of the immune system simultaneously. Systems immunology is then proposed and provide a broader perspective of the immune landscape. This thesis will investigate the human immune responses against cancers and microbes with a focus on T cells using systems-level immunomonitoring. In paper I, we recruited a pan-cancer cohort of patients with pediatric solid tumors and performed systems-level immunomonitoring. We found that tumor type and age of patient have balanced contributions to the immune responses against tumor. The T cell clonal expansion is rare prior to treatment but can be elicited by treatments. Those clonally expanded T cells, although less abundant in children, are transcriptionally comparable to those in adults with more immunogenic cancers. This study demonstrated the possibility for precision immunotherapies for children with cancer. In paper II, we studied the immune development of the extremely preterm infants. We described a delayed immune normalization in the most immature infants with gestational age 22-24 weeks, but they follow the similar trajectory as indicated by term controls. We also demonstrated a strong influence of mother’s own milk, but not pasteurized donor milk, in promoting healthy immune development comparable to healthy term infants. The different immune developments in infants fed with mother’s own milk and donor milk are manifested by NK cell development. Neither of the differences can be explained by microbiome composition, indicating direct effects of bioactive components in mother’s own milk. In paper III, we demonstrated that a deficiency of bifidobacteria, particularly the depletion of genes essential for human milk oligosaccharide (HMO) utilization in the metagenome, is linked to systemic inflammation and immune dysregulation in early life. In breastfed infants supplemented with Bifidobacterium infantis (B.infantis), which possesses all HMO-utilization genes, intestinal Th2 and Th17 cytokines were suppressed while IFN-β was induced. Fecal water from B.infantis-supplemented infants contained abundant indolelactate (ILA) and indole-3-lactic acid, which upregulated immunoregulatory galectin-1 in Th2 and Th17 cells and induced a skewed Th1 polarization. This provides a functional connection between beneficial microbes and immunoregulation during the first months of life. In paper IV, we studied acute COVID-19 patients with longitudinal immunomonitoring and found an immune trajectory from admission to recovery that is shared in those patients. We also described an IFNγ-eosinophil axis activated right before lung hyperinflammation. In paper V, we investigated severe long COVID patients with organ damage or dysfunction. By performing systems-level immunomonitoring, we identified elevated serological responses to SARS-CoV-2 in severe Long COVID, indicative of chronic antigen stimulation. Elevated serologic responses to SARS-CoV-2 were inversely correlated with clonally expanded memory CD8+ T cells with specificity to SARS-CoV-2. This suggests that restrained SARS-CoV-2-specific clonal expansion enables viral persistence, chronic antigen exposure, and elevated IgG responses

Controlling shareholder share pledging and Enterprise Cost Stickiness: Evidence from Chinese Firms

Using a sample of Chinese enterprises pledge during the period 2008-2017, this paper investigates the cost management behavior of enterprises during the pledge period of major shareholders’ stock rights. Our findings show that with the increase of the equity pledge rate, the cost stickiness of enterprises is enhanced. Further analysis shows that the behavior that the controlling shareholder invests the equity pledge funds to a third party weakens the cost stickiness of the enterprise. We further contribute to the literature on sticky cost and equity pledge by discussing the strategic choices of major shareholders to avoid risks during the equity pledge period

JPEG reversible data hiding method based on optimal DCT frequency embedding

Joint photographic experts group (JPEG) images are widely used on the Internet due to their ability to maintain good picture quality while requiring less storage space.Reversible data hiding (RDH) techniques for JPEG images enable the hiding and extraction of secret information while allowing for lossless restoration of the original image.RDH is of great significance in file management and image authentication.However, many existing RDH methods result in a significant increase in the storage space of the encoded image after embedding secret information.For methods based on discrete cosine transform (DCT) coefficient embedding, the key issue that affects the performance of reversible information hiding in JPEG images is how to select the frequency band position.A reversible information hiding method for JPEG images was proposed, based on optimal DCT frequency embedding.The entropy decoded JPEG image was divided into 8×8 non-overlapping DCT blocks.The average texture complexity of each DCT block was calculated and ordered in ascending order.Then the alternating current (AC) in adjacent DCT blocks was paired pairwise.By satisfying the capacity of the information to be embedded, the optimal AC coefficient frequency position set was obtained from the distortion cost function of the AC coefficient frequency.The secret information was embedded according to the designed two-dimensional histogram mapping strategy.Experimental results demonstrate that the proposed method can reduce the expansion of the loaded image file’s storage size compared to existing methods, while maintaining good visual quality of the cover image