Microstructural analysis of skeletal muscle force generation during aging.

Human aging results in a progressive decline in the active force generation capability of skeletal muscle. While many factors related to the changes of morphological and structural properties in muscle fibers and the extracellular matrix (ECM) have been considered as possible reasons for causing age-related force reduction, it is still not fully understood why the decrease in force generation under eccentric contraction (lengthening) is much less than that under concentric contraction (shortening). Biomechanically, it was observed that connective tissues (endomysium) stiffen as ages, and the volume ratio of connective tissues exhibits an age-related increase. However, limited skeletal muscle models take into account the microstructural characteristics as well as the volume fraction of tissue material. This study aims to provide a numerical investigation in which the muscle fibers and the ECM are explicitly represented to allow quantitative assessment of the age-related force reduction mechanism. To this end, a fiber-level honeycomb-like microstructure is constructed and modeled by a pixel-based Reproducing Kernel Particle Method (RKPM), which allows modeling of smooth transition in biomaterial properties across material interfaces. The numerical investigation reveals that the increased stiffness of the passive materials of muscle tissue reduces the force generation capability under concentric contraction while maintains the force generation capability under eccentric contraction. The proposed RKPM microscopic model provides effective means for the cellular-scale numerical investigation of skeletal muscle physiology. NOVELTY STATEMENT: A cellular-scale honeycomb-like microstructural muscle model constructed from a histological cross-sectional image of muscle is employed to study the causal relations between age-associated microstructural changes and age-related force loss using Reproducing Kernel Particle Method (RKPM). The employed RKPM offers an effective means for modeling biological materials based on pixel points in the medical images and allow modeling of smooth transition in the material properties across interfaces. The proposed microstructure-informed muscle model enables quantitative evaluation on how cellular-scale compositions contribute to muscle functionality and explain differences in age-related force changes during concentric, isometric and eccentric contractions

Medication adherence and costs of medical care among patients with Parkinson’s disease: an observational study using electronic medical records

Background: Adherence to antiparkinsonian drugs (APDs) is critical for patients with Parkinson’s disease (PD), for which medication is the main therapeutic strategy. Previous studies have focused on specific disorders in a single system when assessing clinical factors affecting adherence to PD treatment, and no international comparative data are available on the medical costs for Chinese patients with PD. The present study aimed to evaluate medication adherence and its associated factors among Chinese patients with PD using a systematic approach and to explore the impact of adequate medication adherence on direct medical costs. Methods: A retrospective analysis was conducted using the electronic medical records of patients with PD from a medical center in China. Patients with a minimum of two APD prescriptions from January 1, 2016 to August 15, 2018 were included. Medication possession ratio (MPR) and proportion of days covered were used to measure APD adherence. Multiple linear regression analysis was used to identify factors affecting APD adherence. Gamma regression analysis was used to explore the impact of APD adherence on direct medical costs. Results: In total, 1,712 patients were included in the study, and the mean MPR was 0.68 (± 0.25). Increased number of APDs and all medications, and higher daily levodopa-equivalent doses resulted in higher MPR (mean difference [MD] = 0.04 [0.03–0.05]; MD = 0.02 [0.01–0.03]; MD = 0.03 [0.01–0.04], respectively); combined digestive system diseases, epilepsy, or older age resulted in lower MPR (MD = -0.06 [-0.09 to -0.03]; MD = -0.07 [-0.14 to -0.01]; MD = -0.02 [-0.03 to -0.01], respectively). Higher APD adherence resulted in higher direct medical costs, including APD and other outpatient costs. For a 0.3 increase in MPR, the two costs increased by $34.42 ($25.43–$43.41) and$14.63 ($4.86–$24.39) per year, respectively. Conclusions: APD adherence rate among Chinese patients with PD was moderate and related primarily to age, comorbidities, and healthcare costs. The factors should be considered when prescribing APDs

Interactions between inertial particles and shocklets in compressible turbulent flow

Numerical simulations are conducted to investigate the dynamics of inertial particles being passively convected in a compressible homogeneous turbulence. Heavy and light particles exhibit very different types of non-uniform distributions due to their different behaviors near shocklets. Because of the relaxation nature of the Stokes drag, the heavy particles are decelerated mainly at downstream adjacent to the shocklets and form high-number-density clouds. The light particles are strongly decelerated by the added-mass effect and stay in the compression region for a relatively long time period. They cluster into thin filament structures near shocklets

Negative regulation of TLR signaling in myeloid cells--implications for autoimmune diseases

Toll-like receptors (TLR) are transmembrane pattern recognition receptors that recognize microbial ligands and signal for production of inflammatory cytokines and type I interferon in macrophages and dendritic cells (DC). Whereas TLR-induced inflammatory mediators are required for pathogen clearance, many are toxic to the host and can cause pathological inflammation when over-produced. This is demonstrated by the role of TLR-induced cytokines in autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Because of the potent effects of TLR-induced cytokines, we have diverse mechanisms to dampen TLR signaling. Here, we highlight three pathways that participate in inhibition of TLR responses in macrophages and DC, and their implications in autoimmunity; A20, encoded by the TNFAIP3 gene, Lyp encoded by the PTPN22 gene, and the BCAP/PI3K pathway. We present new findings that Lyp promotes TLR responses in primary human monocytes and that the autoimmunity risk Lyp620W variant is more effective at promoting TLR-induced interleukin-6 than the non-risk Lyp620R protein. This suggests that Lyp serves to downregulate a TLR inhibitory pathway in monocytes, and we propose that Lyp inhibits the TREM2/DAP12 inhibitory pathway. Overall, these pathways demonstrate distinct mechanisms of negative regulation of TLR responses, and all impact autoimmune disease pathogenesis and treatment

Time trend analysis of thyroid cancer surgery in China: single institutional database analysis of 15,000 patients

n/

Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma

BackgroundWe explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood.MethodsWe integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments.ResultsAnalysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness.ConclusionSRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients

Viral Diversity and Its Relationship With Environmental Factors at the Surface and Deep Sea of Prydz Bay, Antarctica

A viral metagenomic analysis of five surface and two bottom water (878 meters below surface, mbs, and 3,357 mbs) samples from Prydz Bay, was conducted during February–March 2015. The results demonstrated that most of the DNA viruses were dsDNA viruses (79.73–94.06%, except at PBI1, 37.51%). Of these, Caudovirales (Siphoviridae, Myoviridae, and Podoviridae) phages were most abundant in surface seawater (67.67–71.99%), while nucleocytoplasmic large DNA viruses (NCLDVs) (Phycodnaviridae, Mimiviridae, and Pandoraviridae accounted for >30% of dsDNA viruses) were most abundant in the bottom water (3,357 mbs). Of the ssDNA viruses, Microviridae was the dominant family in PBI2, PBI3, PBOs, and PBI4b (57.09–87.55%), while Inoviridae (58.16%) was the dominant family in PBI1. Cellulophaga phages (phi38:1 and phi10:1) and Flavobacterium phage 11b, infecting the possible host strains affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes, were abundant in surface water dsDNA viromes. The long contig (PBI2_1_C) from the viral metagenomes were most similar to the genome architectures of Cellulophaga phage phi10:1 and Flavobacterium phage 11b from the Arctic Ocean. Comparative analysis showed that the surface viral community of Prydz Bay could be clearly separated from other marine and freshwater environments. The deep sea viral community was similar to the deep sea viral metagenome at A Long-term Oligotrophic Habitat Assessment Station (ALOHA, at 22°45′N, 158°00′W). The multivariable analysis indicated that nutrients probably played an important role in shaping the local viral community structure. This study revealed the preliminary characteristics of the viral community in Prydz Bay, from both the surface and the deep sea. It provided evidence of the relationships between the virome and the environment in Prydz Bay and provided the first data from the deep sea viral community of the Southern Ocean

Life cycle assessment of energy consumption and environmental emissions for cornstalk-based ethyl levulinate

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.This study analysed the sustainability of fuel-ethyl levulinate (EL) production along with furfural, as a by-product, from cornstalk in China. A life cycle assessment (LCA) was conducted using the SimaPro software to evaluate the energy consumption (EC), greenhouse gas (GHG) and criteria emissions, from cornstalk growth to EL utilisation. The total life cycle EC was found to be 4.54MJ/MJ EL, of which 94.7% was biomass energy. EC in the EL production stage was the highest, accounting for 96.8% of total EC. Fossil EC in this stage was estimated to be 0.095 MJ/MJ, which also represents the highest fossil EC throughout the life cycle (39.5% of the total). The ratio of biomass to fossil EC over the life cycle was 17.9, indicating good utilisation of renewable energy in cornstalk-based EL production. The net life cycle GHG emissions were 96.6 g CO2-eq/MJ. The EL production stage demonstrated the highest GHG emissions, representing 53.4% of the total positive amount. Criteria emissions of carbon monoxide (CO) and particulates ≤ 10 um (PM10) showed negative values, of -3.15 and -0.72 g/MJ, respectively. Nitrogen oxides (NOx) and sulphur dioxide (SO2) emissions showed positive values of 0.33 and 0.28 g/MJ, respectively, mainly arising from the EL production stage. According to the sensitivity analysis, increasing or removing the cornstalk revenue in the LCA leads to an increase or decrease in the EC and environmental emissions while burning cornstalk directly in the field results in large increases in emissions of NMVOC, CO, NOx and PM10 but decreases in fossil EC, and SO2 and GHG emissions.This study was supported by the National Natural Science Foundation of China (51506049), the National High Technology Research and Development Program of China (863 Program) (2012AA051802) and the Henan Province Foundation and Advanced Technology Research Project (132300413218)

Simultaneous Prediction, Determination, and Extraction of Four Polycyclic Aromatic Hydrocarbons in the Environment Using a UCON–NaH2PO4 Aqueous Two-Phase Extraction System Combined with High-Performance Liquid Chromatography-Ultraviolet Detection

In this paper, a new aqueous two-phase extraction system(ATPES) consisting of UCON (poly(ethylene glycol-ran-propylene glycol) monobutyl ether)–NaH2PO4 was established, and four trace polycyclic aromatic hydrocarbons (PAHs: fluorene, anthracene, pyrene and phenanthrene) in water and soil were analyzed by high-performance liquid chromatography (HPLC)–ultraviolet detection. In the multi-factor experiment, the central composite design (CCD) was used to determine the optimum technological conditions. The final optimal conditions were as follows: the concentration of UCON was 0.45 g·mL−1, the concentration of NaH2PO4 was 3.5 mol·L−1, and the temperature was 30 °C. The recovery of the four targets was 98.91–99.84% with a relative standard deviation of 0.3–2.1%. Then UCON recycling and cyclic tests were designed in the experiment, and the results showed that the recovery of PAHs gradually increased in the three extractions because of the remaining PAHs in the salt phase of last extraction. The recovery of PAHs in the UCON recycling test was less than that in the extraction test due to the wastage of UCON. In addition, a two-phase aqueous extraction model was established based on the random forest (RF) model. The results obtained were compared with the experimental data, and the root mean square error (RMSE) was 0.0371–0.0514 and the correlation coefficient R2 was 96.20–98.53%, proving that the model is robust and reliable

Background suppression of small target image based on fast local reverse entropy operator

Background suppression is vitally important for the small target detection, which aims to enhance targets and improve the signal‐to‐noise ratio of small target images. Consequently, the study proposes a background suppression approach based on the fast local reverse entropy operator, which is designed according to the fact that the appearance of a small target could result in the great change of the value of local reverse entropy in the local region. The operator is adopted to suppress complex backgrounds of small target images in order to enhance small targets, and then bring about high probabilities of detection and low probabilities of false alarm in the small target detection. Both quantitative and qualitative analyses contribute to confirm the validity and efficiency of the proposed approach