p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of ...osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53
, p53
, and p53
mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.
Vision-based approaches are widely used in steel crack detection. After processing the images taken by the camera, the superficial defects can be detected. Due to the common limitation of the nature ...of photographic images, internal features of objects cannot be fully discovered. In order to overcome the drawbacks of vision-based methods, this work presents an approach for detecting cracks in infrared thermal imaging steel sheets using Convolutional Neural Networks (CNN). Firstly, a horizontal heat conduction method is researched to thermally excite the surface of the steel sheet, and a rolling electric heating device is developed to be a thermal excitation source. Secondly, we analyze the temperature difference between normal area and different crack depths, and study the influence of temperature change. Thirdly, 3000 infrared thermograms labeled for penetrating cracks, non-penetrating cracks, and surface scratches are fabricated into a databank. Then, the CNN is trained and validated on the data bank. Finally, improving the original Faster Region-based Convolutional Neural Network (Faster R-CNN) network, the feature maps of multiple levels in the feature extraction network are aggregated, and the anchor selection scheme of the Region Proposal Network (RPN) is adjusted from 9 to 25. The robustness of the improved Faster R-CNN is demonstrated by evaluating the detection results on the 125 images outside of the data bank, the accuracy and Mean Average Precision (mAP) are 95.54% and 92.41%, respectively, which outperform the original algorithm by increasing the accuracy of 3.18% and mAP of 1.88%.
We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH ...treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.
Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with ...acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.
Immunoassays provide a high-throughput method for monitoring pesticides in foods and the environment. Due to easy generation and capable of being manipulated, chicken single-chain variable fragment ...(scFv) is attractive in the development of immunoassays for pesticides. Two scFvs (X1 and X2) against the insecticide carbaryl were generated from a chicken immunized with hapten C1 conjugated to keyhole limpet hemocyanin and fused with alkaline phosphatase (AP) to develop a rapid one-step enzyme-linked immunosorbent assay for this pesticide. X2-AP showed higher binding affinity to carbaryl than X1-AP. The X2-AP-based ELISA had a half-maximum signal inhibition concentration of 15 ng mL−1 and a limit of detection of 1.6 ng mL−1. This assay showed negligible cross-reactivity with other carbamate pesticides (<0.1%) and low cross-reactivity with 1-naphthol (5%). The average recoveries of carbaryl spiked in soil, apple and pear samples by the one-step assay ranged from 90% to 114% and agreed well with those of high-performance liquid chromatography. The chicken scFv-based assay showed promise as a high-throughput screening tool for carbaryl in environmental and food matrices.
•Two anti-carbaryl chicken scFvs were generated and genetically fused with alkaline phosphatase.•A rapid and sensitive one-step immunoassay based on a scFv-AP was developed for carbaryl.•The recovery of carbaryl from spiked samples by the scFv-AP based ELISA ranged from 90% to 114%.
A novel deep eutectic solvent-magnetic molecularly imprinted polymer (DES-MMIP) for the specific removal of oxalic acid (OA) was prepared by an environmentally friendly deep eutectic solvent, ...consisting of betaine, citric acid, and glycerol, which acted as the functional monomer for polymerization. The structure and morphology of DES-MMIPs were studied by X-ray diffraction, scanning and transmission electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. DES-MMIPs had a core–shell structure, with magnetic iron oxide as the core, and showed good thermal stability and high adsorption capacity (18.73 mg/g) for OA. The adsorption process of OA by DES-MMIPs followed the pseudo-second-order kinetic model and Langmuir isotherm model. DES-MMIPs had significant selectivity for OA and their imprinting factor was 3.26. When applied to real samples, high performance liquid chromatography analysis showed that DES-MMIPs could remove OA from both spinach and blood serum. These findings provide potential methods for removal of OA from vegetables and for specific removal of OA in renal dialysis.
Graphical abstract
ObjectiveDo-not-attempt-resuscitation (DNAR) orders are designed to allow patients to opt out of receiving cardiopulmonary resuscitation in the event of a cardiac arrest. While DNAR has become a ...standard component of medical care, there is limited research available specifically focusing on DNAR orders in the context of emergency departments in China. This study aimed to fill that gap by examining the factors related to DNAR orders among patients in the emergency department of a general tertiary teaching hospital in China.DesignRetrospective observational study.SettingEmergency department.ParticipantsThis study and analysis on adult patients with DNAR or no DNAR data between 1 January 2022 and 1 January 2023 in the emergency department of a large academic comprehensive tertiary teaching hospital. A total of 689 were included in our study.Primary outcome measuresWhether the patient received DNAR was our dependent variable.ResultsAmong the total patients, 365 individuals (53.0%) had DNAR orders. The following variables, including age, sex, age-adjusted Charlson comorbidity index (ACCI), primary diagnosis of cardiogenic or cancer related, history of neurological dysfunction or cancer, were independently associated with the difference between the DNAR group and the no DNAR group. Furthermore, there were significant statistical differences observed in the choice of DNAR among patients with different stages of cancer.ConclusionsIn comparison to the no DNAR group, patients with DNAR were characterised by being older, having a higher proportion of female patients, higher ACCI scores, a lower number of patients with a primary diagnosis of cardiogenic and a higher number of patients with a primary diagnosis of cancer related, history of neurological dysfunction or cancer.
Neuropathic pain is a common clinical condition. Current treatments are often inadequate, ineffective, or produce potentially severe adverse effects. Understanding the mechanisms that underlie the ...development and maintenance of neuropathic pain will be helpful in identifying new therapeutic targets and developing effective strategies for the prevention and/or treatment of this disorder. The genesis of neuropathic pain is reliant, at least in part, on abnormal spontaneous activity within sensory neurons. Therefore, voltage-gated sodium channels, which are essential for the generation and conduction of action potentials, are potential targets for treating neuropathic pain. However, preclinical studies have shown unexpected results because most pain-associated voltage-gated channels in the dorsal root ganglion are down-regulated after peripheral nerve injury. The role of dorsal root ganglion voltage-gated channels in neuropathic pain is still unclear. In this report, we describe the expression and distribution of voltage-gated sodium channels in the dorsal root ganglion. We also review evidence regarding changes in their expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. We finally discuss their potential involvement in neuropathic pain.
This paper is an attempt to study the performance of concrete filled steel tubular (CFST) members with square sections under both loading and chloride corrosion. A total of 28 specimens, including 17 ...stub columns and 11 beams, were tested. The main parameters were loading ratio (from 0 to 0.75) during corrosion, as well as corrosion condition (no corrosion, and fully or half immersed into corrosive solution, respectively). According to the test, the effects of both loading and corrosion on the behaviour of CFST and reference hollow steel tubular members were analyzed. Comparisons between the predicted ultimate strength by using the existing codes of DBJ/T13-51-2010 and EC4-2004 and the testing results were proposed.
► Studies of CFST members under both loading and chloride corrosion. ► CFST stub columns and beams tests. ► Effects of loading ratio and corrosion conditions.
Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic ...peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.
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