C1q/TNF-related protein 3 (CTRP3) and 9 (CTRP9) concentrations are decreased in patients with heart failure and are associated with increased morbidity and mortality.

BACKGROUND: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality. METHODS: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. CTRP3 and CTRP9 levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Both CTRP3 and CTRP9 concentrations were significantly decreased in the HFrEF group compared to the control group (p \u3c 0.001). Moreover, patients with higher New York Heart Association class had significantly lower CTRP3 or CTRP9 concentrations. Correlation analysis revealed that CTRP3 and CTRP9 levels were positively related with LVEF% (CTRP3, r = 0.556, p \u3c 0.001; CTRP9, r = 0.526, p \u3c 0.001) and negatively related with NT-proBNP levels (CTRP3, r = - 0.454, p \u3c 0.001; CTRP9, r = - 0.483, p \u3c 0.001). After a follow up for 36 months, after adjusted for age, LVEF and NT-proBNP, we observed that CTRP3 or CTRP9 levels below the 25th percentile was a predictor of total mortality (CTRP3,HR:1.93,95%CI1.03~3.62,P = 0.042;CTRP9,HR:1.98,95%CI:1.02~3.85,P = 0.044) and hospitalizations (CTRP3,HR:2.34,95% CI:1.43~3.82,P = 0.001;CTRP9,HR:2.67,95%CI:1.58~4.50,P \u3c 0.001). CONCLUSIONS: CTRP3 and CTRP9 are decreased in patients with HFrEF, proportionate to disease severity, and each is associated with increased morbidity and mortality. TRIAL REGISTRATION: NCT01372800 . Registered May 2011

Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation

Objective: Rheumatoid arthritis (RA) is associated with chronic inflammation. The suppression of inflammation is key to the treatment of RA. Glucocorticoids (GCs) are classical anti-inflammatory drugs with several disadvantages such as poor water solubility and low specificity in the body. These disadvantages are the reasons for the quick elimination and side effects of GCs in vivo. Micelles are ideal carriers for GCs delivery to inflamed synovium. We set out to improve the targeting and pharmacokinetic profiles of GCs by preparing a targeting micelle system. Methods: In this study, natural chlosterol (CC) and folic acid (FA) were used to fabricate polysialic acid (PSA) micelles for the targeted delivery of Dexamethasone (Dex). The biodistribution and therapeutic efficacy of the resulting micelles were evaluated in vitro and in vivo. Results: PSA-CC and FA-PSA-CC micelles showed a size below 100 nm and a moderate negative charge. PSA-CC and FA-PSA-CC micelles could also enhance the intracellular uptake of Dex and the suppression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vitro and in vivo. Arthritis mice showed reduced paw thickness and clinical arthritis index using PSA-CC and FA-PSA-CC micelle treatment. Micellized Dex demonstrated a 4 ∼ 5 fold longer elimination half-life and a 2 ∼ 3 folds higher bioavailability than commercial Dex injection. FA modification significantly improved the anti-inflammatory efficacy of PSA-CC micelles. Conclusion: FA-PSA-CC micelles demonstrated significant advantages in terms of the suppression of inflammation and the treatment of inflammatory arthritis. These reliable and stable micelles possess a high potential to be transferred for clinical use

Untargeted LC–MS/MS-Based Metabolomic Profiling for the Edible and Medicinal Plant Salvia miltiorrhiza Under Different Levels of Cadmium Stress

Salvia miltiorrhiza, a medicinal and edible plant, has been extensively applied to treat cardiovascular diseases and chronic hepatitis. Cadmium (Cd) affects the quality of S. miltiorrhiza, posing serious threats to human health. To reveal the metabolic mechanisms of S. miltiorrhiza's resistance to Cd stress, metabolite changes in S. miltiorrhiza roots treated with 0 (CK), 25 (T1), 50 (T2) and 100 (T3) mg kg−1 Cd by liquid chromatography coupled to mass spectrometry (LC–MS/MS) were investigated. A total of 305 metabolites were identified, and most of them were amino acids, organic acids and fatty acids, which contributed to the discrimination of CK from the Cd-treated groups. Among them, S. miltiorrhiza mainly upregulated o-tyrosine, chorismate and eudesmic acid in resistance to 25 mg kg−1 Cd; DL-tryptophan, L-aspartic acid, L-proline and chorismite in resistance to 50 mg kg−1 Cd; and L-proline, L-serine, L-histidine, eudesmic acid, and rosmarinic acid in resistance to 100 mg kg−1 Cd. It mainly downregulated unsaturated fatty acids (e.g., oleic acid, linoleic acid) in resistance to 25, 50, and 100 mg kg−1 Cd and upregulated saturated fatty acids (especially stearic acid) in resistance to 100 mg kg−1 Cd. Biosynthesis of unsaturated fatty acids, isoquinoline alkaloid, betalain, aminoacyl-tRNA, and tyrosine metabolism were the significantly enriched metabolic pathways and the most important pathways involved in the Cd resistance of S. miltiorrhiza. These data elucidated the crucial metabolic mechanisms involved in S. miltiorrhiza Cd resistance and the crucial metabolites that could be used to improve resistance to Cd stress in medicinal plant breeding

Sluggish and Chemically-Biased Interstitial Diffusion in Concentrated Solid Solution Alloys: Mechanisms and Methods

Interstitial diffusion is a pivotal process that governs the phase stability and irradiation response of materials in non-equilibrium conditions. In this work, we study sluggish and chemically-biased interstitial diffusion in Fe-Ni concentrated solid solution alloys (CSAs) by combining machine learning (ML) and kinetic Monte Carlo (kMC), where ML is used to accurately and efficiently predict the migration energy barriers on-the-fly. The ML-kMC reproduces the diffusivity that was reported by molecular dynamics results at high temperatures. With this powerful tool, we find that the observed sluggish diffusion and the "Ni-Ni-Ni"-biased diffusion in Fe-Ni alloys are ascribed to a unique "Barrier Lock" mechanism, whereas the "Fe-Fe-Fe"-biased diffusion is influenced by a "Component Dominance" mechanism. Inspired by the mentioned mechanisms, a practical AvgS-kMC method is proposed for conveniently and swiftly determining interstitial-mediated diffusivity by only relying on the mean energy barriers of migration patterns. Combining the AvgS-kMC with the differential evolutionary algorithm, an inverse design strategy for optimizing sluggish diffusion properties is applied to emphasize the crucial role of favorable migration patterns.Comment: 30 pages,9 figure

Epigenetic regulation of programmed cell death in hypoxia-induced pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a severe progressive disease that may cause early right ventricular failure and eventual cardiac failure. The pathogenesis of PAH involves endothelial dysfunction, aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs), and vascular fibrosis. Hypoxia has been shown to induce elevated secretion of vascular endothelial growth factor (VEGF), leading to the development of hypoxic PAH. However, the molecular mechanisms underlying hypoxic PAH remain incompletely understood. Programmed cell death (PCD) is a natural cell death and regulated by certain genes. Emerging evidence suggests that apoptotic resistance contributes to the development of PAH. Moreover, several novel types of PCD, such as autophagy, pyroptosis, and ferroptosis, have been reported to be involved in the development of PAH. Additionally, multiple diverse epigenetic mechanisms including RNA methylation, DNA methylation, histone modification, and the non-coding RNA molecule-mediated processes have been strongly linked to the development of PAH. These epigenetic modifications affect the expression of genes, which produce important changes in cellular biological processes, including PCD. Consequently, a better understanding of the PCD processes and epigenetic modification involved in PAH will provide novel, specific therapeutic strategies for diagnosis and treatment. In this review, we aim to discuss recent advances in epigenetic mechanisms and elucidate the role of epigenetic modifications in regulating PCD in hypoxia-induced PAH

Imaging Chromophores With Undetectable Fluorescence by Stimulated Emission Microscopy

Fluorescence, that is, spontaneous emission, is generally more sensitive than absorption measurement, and is widely used in optical imaging. However, many chromophores, such as haemoglobin and cytochromes, absorb but have undetectable fluorescence because the spontaneous emission is dominated by their fast non-radiative decay. Yet the detection of their absorption is difficult under a microscope. Here we use stimulated emission, which competes effectively with the nonradiative decay, to make the chromophores detectable, and report a new contrast mechanism for optical microscopy. In a pump-probe experiment, on photoexcitation by a pump pulse, the sample is stimulated down to the ground state by a time-delayed probe pulse, the intensity of which is concurrently increased. We extract the miniscule intensity increase with shot-noise-limited sensitivity by using a lock-in amplifier and intensity modulation of the pump beam at a high megahertz frequency. The signal is generated only at the laser foci owing to the nonlinear dependence on the input intensities, providing intrinsic three-dimensional optical sectioning capability. In contrast, conventional one-beam absorption measurement exhibits low sensitivity, lack of three-dimensional sectioning capability, and complication by linear scattering of heterogeneous samples. We demonstrate a variety of applications of stimulated emission microscopy, such as visualizing chromoproteins, non-fluorescent variants of the green fluorescent protein, monitoring lacZ gene expression with a chromogenic reporter, mapping transdermal drug distributions without histological sectioning, and label-free microvascular imaging based on endogenous contrast of haemoglobin. For all these applications, sensitivity is orders of magnitude higher than for spontaneous emission or absorption contrast, permitting nonfluorescent reporters for molecular imaging.Chemistry and Chemical Biolog

Acceleration behaviors of Fermi accelerator model excited by Van der Pol oscillator

In this paper, we investigate on dynamics of a generalized Fermi accelerator model with a moving wall described by a nonlinear Van der Pol oscillator. Different acceleration behaviors appear due to the discontinuity brought by impact and the stationary periodic excitation of the moving wall. Utilizing the theory of discontinuous dynamical systems, acceleration mechanism of the particle is studied and the analytical conditions for stick motion and grazing motion are obtained. By the use of generic mappings between different boundaries including stick and non-stick motions, periodic motions of the Fermi accelerator can be constructed, and corresponding local stability and bifurcations can be discussed according to mapping dynamics. Finally, different acceleration behaviors including periodic, chatter and stick motions are presented and illustrated

Advances in Research of Characteristics and Removal of Microplastics in Sewage Treatment Plants

Microplastic pollution has become a worldwide issue. The discharge of sewage treatment plants (STPs) or wastewater treatment plant (WWTPs) is an important way for microplastics to enter the environment. This study reviewed the sources and occurrence characteristics (type, size, color and components) of microplastics in domestic and foreign sewage plants. It elaborated the removal principles of microplastics by primary, secondary and tertiary treatments. In addition, the removal effects of various treatment units and different processes on microplastics were summarized. In the future, the removal mechanism of microplastics in sewage treatment plants should be discussed in more depth, so as to further improve the removal rate of microplastics by optimizing and transforming traditional sewage treatment processes. Therefore, it is necessary to develop new technologies/processes specifically for the removal of microplastics and promote them to practical applications

Generative Models for Data Synthesis

Finding large quantities of high-quality data to train neural networks is one of the most challenging aspects for researchers since privacy restrictions and associated financial obligations make it difficult to gather the data. In recent years, Generative Adversarial Networks (GANs) have been extensively used in the generation of different types of datasets. Despite this, we cannot control the attributes that will be associated with a data sample generated by GANs. Combining GANs with Variational Autoencoders (VAEs) is an effective way of obtaining outputs which have the desired attributes. Our study examined the sampling capacity and quality of VAE and VAE-GAN for MNIST and Fashion MNIST datasets. Additionally, we introduce a new metric, Transformer Score (TS), to determine the quality of the generated data. It is based on a vision transformers network and demonstrates superiority over Inception Score

The efficacy and safety of Xuefu Zhuyu Decoction Combined Mifepristone in the treatment of Uterine leiomyoma：A protocol systematic review and meta-analysis

Abstract Background Uterine leiomyoma (UL) is a common severe gynecological issue. In China, Xuefu Zhuyu Decoction (XFZYD), combined with Mifepristone, is widely used in the treatment of UL. However, their combined effectiveness and safety for this purpose have not yet been explored. Objective This systematic review aims to evaluate the effectiveness and safety of XFZYD combined with Mifepristone as a method of treatment for UL. Methods We searched the following 7 databases: 3 English medical databases (PubMed, EMBASE, Cochrane Library), and 4 Chinese medical databases (Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and the Wanfang database). The primary outcome was the effect of XFZYD combined with Mifepristone on the effective rate, uterine leiomyoma volume (ULV), and uterine volume (UV) of uterine leiomyoma. Bias risk was assessed using the Cochrane risk of bias tool. The software RevMan5 was used to evaluate the quality of the included studies and process the data. Results: This study will evaluate the efficacy and safety of XFZYD combined with Mifepristone in the treatment of uterine fibroids by evaluating the effective rate, Uterine Leiomyoma volume, and uterine volume, the incidence of estradiol, luteinizing hormone, and other indicators. Conclusion: This study will provide reliable evidence-based evidence for Xuefu Zhuyu Decoction Combined with Mifepristone in the treatment of uterine fibroids