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Musculoskeletal diseases affect over 100 million people globally and are a leading cause of severe, prolonged pain, and disability. Recognized as a clinical emergency, prompt and accurate diagnosis of musculoskeletal disorders is crucial, as delayed identification poses the risk of amputation for patients, and in severe cases, can result in life-threatening conditions such as bone cancer. In this paper, a hybrid model HRD (Human-Resnet50-Densenet121) based on deep learning and human participation is proposed to efficiently identify disease features by classifying X-ray images. Feasibility testing of the model was conducted using the MURA dataset, with metrics such as accuracy, recall rate, F1-score, ROC curve, Cohen's kappa, and AUC values employed for evaluation. Experimental results indicate that, in terms of model accuracy, the hybrid model constructed through a combination strategy surpassed the accuracy of any individual model by more than 4%. The model achieved a peak accuracy of 88.81%, a maximum recall rate of 94%, and the highest F1-score value of 87%, all surpassing those of any single model. The hybrid model demonstrates excellent generalization performance and classification accuracy. [ABSTRACT FROM AUTHOR]

Soil pathogens play important roles in shaping soil microbial diversity and controlling ecosystem functions. Though climate and local environmental factors and their influences on fungal pathogen communities have been examined separately, few studies explore the relative contributions of these factors. This is particularly crucial in eco‐fragile regions, which are more sensitive to environmental changes. Herein we investigated the diversity and community structure of putative soil fungal pathogens in cold and dry grasslands on the Tibetan Plateau, using high‐throughput sequencing. The results showed that steppe soils had the highest diversity of all pathogens and plant pathogens; contrastingly, meadow soils had the highest animal pathogen diversity. Structural equation modelling revealed that climate, plant, and soil had similar levels of influence on putative soil fungal pathogen diversity, with total effects ranging from 52% to 59% (all p < 0.001), with precipitation exhibiting a stronger direct effect than plant and soil factors. Putative soil fungal pathogen community structure gradually changed with desert, steppe, and meadow, and was primarily controlled by the interactions of climate, plant, and soil factors rather than by distinct factors individually. This finding contrasts with most studies of soil bacterial and fungal community structure, which generally report dominant roles of individual environmental factors. [ABSTRACT FROM AUTHOR]

Background: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. Methods: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases. Results: We identified cell cycle inhibitor p27Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3'UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database. Conclusion: Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients. [ABSTRACT FROM AUTHOR]

Inflammation is a key regulator in the progression of atherosclerosis (AS) which extremely affects people's health. Secoisolariciresinol diglucoside (SDG), a plant lignan, is relevant to angiogenesis and cardioprotection against ischemia-reperfusion injury and improves vascular disorders. However, the effect of SDG on cardiovascular disorder is not clear. In the present study, we aimed to investigate the effects of SDG on lipopolysaccharide- (LPS-) stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and elucidate the underlying mechanism. The LPS-stimulated HUVEC cellular model was established. The cell viability, the cell tube formation activity, the nitric oxide (NO) release, the levels of inflammatory cytokine interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α ), the activation of nuclear factor kappa-B (NF- κ B) pathway, and the expression of protein kinase B (Akt) were determined using Cell Counting Kit-8, cell tube-formation assay, western blotting, and enzyme-linked immunosorbent assay. Our results revealed that SDG reduces the angiogenic capacity of HUVECs and inhibited LPS-mediated HUVEC injury and apoptosis. In addition, SDG increased NO release and decreased the levels of IL-1 β , IL-6, and TNF- α in LPS-treated HUVECs. Meanwhile, SDG inhibited the NF- κ B pathway and downregulated Akt expression in LPS-induced HUVECs. Our results indicated that SDG relieves LPS-mediated HUVEC injury by inhibiting the NF- κ B pathway which is partly dependent on the disruption of Akt activation. Therefore, SDG exerts its cytoprotective effects in the context of LPS-treated HUVECs via regulation of the Akt/I κ B/NF- κ B pathway and may be a potential treatment drug for cardiovascular disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Shaoyang Zhang et al.)

Better understanding of the colloidal behaviors of nanomaterials impacted by aquatic chemistry parameters is needed for appropriate evaluation of the environmental risks posed by nanomaterials in natural waters. In the study, the colloidal stability of Fe 3 O 4 magnetic nanoparticles (Fe-MNPs) was evaluated over a range of chemistry characteristics [e.g., pH, dissolved organic matter (DOM), salt types, cationic strength] in six synthetic water samples. The findings from the synthetic water samples were further examined with eight "real world" environmental water samples. Our results demonstrated that DOM fraction, humic acid (HA), promoted suspension of Fe-MNPs more by hydrophobic interactions in addition to ligand exchange and electrostatic effects compared with fulvic acid (FA). Capability of cations to increase aggregation of Fe-MNPs were in the order of Ca 2+  > Mg 2+ >> Na + because of their different degrees of bridging complexation with DOM molecules on particle surfaces. As a key parameter for indicating Fe-MNPs colloidal stability, Zeta (ζ) potentials of Fe-MNPs in these waters samples were well correlated to (R 2  = 0.880, P < 0.001) the contents, types and adsorption forms of DOM and cations. However, several other factors could also affect the hydrodynamic diameter (HDD) of Fe-MNPs in the "real world" environmental waters. It assumed that ampholytic-DOM molecules such as amino acid- and protein-like molecules caused great aggregation of Fe-MNPs. These findings would be helpful for better understanding and evaluating the colloidal behaviors of nanomaterials when they released into natural water environment, thus could shed light on developing relevant pollution control strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)