The value of using heterogeneous detector groups for the development of time-of-flight (TOF) positron emission tomography (PET) systems.

Objective. Much recent attention on positron emission tomography (PET) is the development of time-of-flight (TOF) systems with ever-improving coincidence time resolution (CTR). This is because, when all other factors remain the same, a better CTR leads to images of better statistics and effectively increases the sensitivity of the system. However, detector designs that aggressively improve the CTR often compromise the detection efficiency (DE) and offset the benefit gained. Under this circumstance, in developing a TOF PET system it may be beneficial to employ heterogeneous detector groups to balance the overall CTR and DE of the system. In this study, we examine the potential value of this system design strategy by considering two-dimensional systems that assume several representative ways of mixing two detector groups.Approach. The study is based on computer simulation and specifically considers medium time-resolution (MTR) detectors that have a 528 ps CTR and high time-resolution (HTR) detectors that have a 100 ps CTR and a DE that is 0.7 times that of the MTR detector. We examine contrast recovery, noise, and subjective quality of the resulting images under various ways of mixing the MTR and HTR detectors.Main results. With respect to the traditional configuration that adopts only the HTR detectors, symmetric heterogeneous configurations may offer comparable or better images while using considerably fewer HTRs. On the other hand, asymmetric heterogeneous configurations may allow the use of only a few HTRs for improving image quality locally.Significance. This study demonstrates the value of the proposed system-level design strategy of using heterogeneous detector groups for achieving high effective system sensitivity by factoring into the tradeoff between the CTR and DE of the detector.

KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner.

Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.

Cryptochrome 2 acetylation attenuates its antiproliferative effect in breast cancer.

Breast cancer is the most commonly diagnosed cancer, and its global impact is increasing. Its onset and progression are influenced by multiple cues, one of which is the disruption of the internal circadian clock. Cryptochrome 2 (Cry2) genetic dysregulation may lead to the development of some diseases and even tumors. In addition, post-translational modifications can alter the Cry2 function. Here, we aimed to elucidate the post-translational regulations of Cry2 and its role in breast cancer pathogenesis. We identified p300-drived acetylation as a novel Cry2 post-translational modification, which histone deacetylase 6 (HDAC6) could reverse. Furthermore, we found that Cry2 inhibits breast cancer proliferation, but its acetylation impairs this effect. Finally, bioinformatics analysis revealed that genes repressed by Cry2 in breast cancer were mainly enriched in the NF-κB pathway, and acetylation reversed this repression. Collectively, these results indicate a novel Cry2 regulation mechanism and provide a rationale for its role in breast tumorigenesis.

Comparative Analysis of the Self-Propelled Locomotion of a Pitching Airfoil near the Flat and Wavy Ground.

In this paper, a pitching airfoil near flat and wavy ground is studied by numerical simulations. The kinematic features of the airfoil and the flow field around it are analyzed to reveal unsteady vorticity dynamics of the self-propelled airfoil in ground effect. The optimal pitching periods at different initial heights above flat ground are obtained, which make the pitching airfoil achieve the maximum lift-to-drag ratio. Compared with flat ground, at the same initial height, the optimal pitching periods vary with the shape of ground. The structure and the strength of the wake vortices shedding from the airfoil are adjusted by the wavelength of ground. This leads to the changes of amplitude and occurrence times of the peak and valley of lift and drag force. The results obtained in this study can provide some inspiration for the design of underwater vehicles in the ground effect.

The Role of PPARs in Breast Cancer.

Breast cancer is a malignant tumor with high morbidity and lethality. Its pathogenesis is related to the abnormal expression of many genes. The peroxisome proliferator-activated receptors (PPARs) are a class of ligand-dependent transcription factors in the nuclear receptor superfamily. They can regulate the transcription of a large number of target genes, which are involved in life activities such as cell proliferation, differentiation, metabolism, and apoptosis, and regulate physiological processes such as glucose metabolism, lipid metabolism, inflammation, and wound healing. Further, the changes in its expression are associated with various diseases, including breast cancer. The experimental reports related to "PPAR" and "breast cancer" were retrieved from PubMed since the discovery of PPARs and summarized in this paper. This review (1) analyzed the roles and potential molecular mechanisms of non-coordinated and ligand-activated subtypes of PPARs in breast cancer progression; (2) discussed the correlations between PPARs and estrogen receptors (ERs) as the nuclear receptor superfamily; and (3) investigated the interaction between PPARs and key regulators in several signaling pathways. As a result, this paper identifies PPARs as targets for breast cancer prevention and treatment in order to provide more evidence for the synthesis of new drugs targeting PPARs or the search for new drug combination treatments.

Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells.

Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein which has been reported to bind a variety of pathogens as well as participate in immunoregulation. But the association between the level of DC-SIGNR and lung cancer is unknown. To investigate the clinical diagnostic significance of DC-SIGNR in lung cancer, we investigated serum DC-SIGNR levels in 173 lung cancer patients and 134 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results showed that serum DC-SIGNR levels in lung cancer patients were lower than that in healthy controls (P = 0.0003). A cut-off value of 3.8998 ng/L for DC-SIGNR predicted the presence of lung cancer with 78.03% sensitivity and 49.25% specificity (area under the curve = 0.6212, P = 0.0003). Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). Moreover, the serum concentrations of DC-SIGNR in lung cancer patients also correlated significantly with serum natural killer cells percentage (P = 0.0017). In addition, immunohistochemistry assay demonstrated that the expression of DC-SIGNR in lung tissues of 31 lung cancer patients and 13 tuberculosis patients was significantly lower than that in 18 normal lung tissues (P = 0.0418, 0.0289), and there is no significant difference between tuberculosis tissues and lung cancer tissues (P = 0.2696). These results suggest that DC-SIGNR maybe a promising biological molecule that has the potential for clinical research of lung cancer, whereas its underlying roles are needed to be investigated in further studies.

Relaxin attenuates silica-induced pulmonary fibrosis by regulating collagen type I and MMP-2.

Silicosis is one of the most prevalent occupational lung diseases, but the pathogenic mechanisms of silicosis are largely unknown and an effective treatment is not yet available. In this study, we investigated the potential effects of relaxin (RLX) on fibrosis by an in vitro model involving silica-induced and macrophage-mediated pulmonary fibroblasts. Following pre-treatment with DQ12 quartz, the culture supernatant of human monocytic THP-1 cells was added to human fetal lung fibroblast MRC-5 cells with or without RLX. DQ12 significantly induced an increase of TGFB1 mRNA in THP-1 cells, coinciding with elevated TGF-ß1 protein excretion in the supernatant, but RLX had no effect on DQ12-stimulated TGF-ß1 secretion in THP-1 cells. Furthermore, RLX inhibited the proliferation of MRC-5 cells, and reduced the mRNA level and protein secretion of collagen type I, whereas it increased the mRNA level and protein activity of MMP-2 in MRC-5 cells treated with THP-1 cell culture supernatant. Our data suggest that RLX may inhibit TGF-ß1-mediated fibrosis during the process of silicosis, providing evidence for the protective effect of RLX on silica-induced pulmonary fibrosis.

[Progressing study in treating discogenic low back pain].

Lumbago is a general, frequently and complicated clinical symptom. 60% to 80% in adults suffer from back pain of varying degrees. The pain causing by various pathological changes stimulateing the ache receptor in intervertebral disc is call discogenic low back pain. Along with people knowing more and more about this disease, all kinds of treatment techniques are applied in clinic. But the indication and therapeutic effects are both evidently different. Below is a summary of the therapic method about discogenic low back pain based on international and domestic reference data of recent years and the author's clinical experiences.