Due to the diversity of landforms, an appropriate threshold should be selected for the simplification of different landforms. The distribution of simplified index was obtained by preprocessing the ...terrain data, and the distribution was used as a reference for threshold selection. In order to study the influence of terrain simplification on the prediction of complex electromagnetic environment, a visibility algorithm used in the regular model of terrain and a probability-based power propagation model are proposed. The visibility algorithm used in the regular model of terrain is based on the relationship between planes and triangular planes in three-dimensional space. The visible triangular surfaces and the corresponding visible area of the triangular surfaces in the terrain can be calculated with the visibility algorithm. The probability-based power propagation model uses the results of the visibility algorithm to calculate the propagation probability and calculates the change of receiver power in combination with the radio wave propagation characteristics. The spatial visibility algorithm and the probability-based power propagation model can be applied to the complex electromagnetic environment to analyze the influence of terrain simplification on prediction accuracy. The minimum error between the simulation result of the probability-based power propagation model and the Wireless InSite simulation result is 0.5018dB, and the average error is 1.5039dB.
The deficit of fragile X messenger ribonucleoprotein (FMRP) leads to intellectual disability in human and animal models, which also leads to desensitization of pain after nerve injury. Recently, it ...was shown that the protein arginine methyltransferases 1 (PRMT1) regulates the phase separation of FMRP. However, the role of PRMT1 in pain regulation has been less investigated. Here we showed that the downregulation of PRMT1 in the anterior cingulate cortex (ACC) contributes to the development of peripheral pain hypersensitivity. We observed that the peripheral nerve injury decreased the expression of PRMT1 in the ACC; knockdown of the PRMT1
shRNA in the ACC decreased the paw withdrawal thresholds (PWTs) of naïve mice. Moreover, the deficits of FMRP abolished the effects of PRMT1 on pain sensation. Furthermore, overexpression of PRMT1 in the ACC increased the PWTs of mice with nerve injury. These observations indicate that the downregulation of cingulate PRMT1 was necessary and sufficient to develop peripheral hypersensitivity after nerve injury. Thus, we provided evidence that PRMT1 is vital in regulating peripheral pain hypersensitivity after nerve injury
the FMRP.
Retinal nerve fiber layer (RNFL) thickness (RT), which can reflect the status of the retinal optic nerve cells, may be affected in patients with Alzheimer's disease (AD). There are few studies on the ...correlation of RT of patients with AD (AD-RT) with clinical symptoms of various cognitive domains, neuropsychiatric symptoms, and activities of daily living (ADL). This study is to investigate the relationships between RT and the abovementioned clinical symptoms of AD.
A total of 96 patients with AD were included in this study. RT was measured in these patients using optical coherence tomography (OCT). Demographic variables, RT, and clinical symptoms were compared between the normal and the abnormal AD-RT groups. Clinical symptoms, including cognitive symptoms, neuropsychiatric symptoms, and ADL, were evaluated using a series of rating scales.
The relationships between RT and cognitive symptoms scores were analyzed in patients with AD. Reduced RT was found in 54.4% of patients with AD. The average RT, RT of the superior 1/2 quadrant, and RT of the inferior 1/2 quadrant of both eyes were all significantly decreased in the abnormal AD-RT group (
< 0.001). Overall cognitive function and performance in multiple cognitive domains, including memory, language, attention, and executive function, were also significantly impaired in the abnormal AD-RT group (
< 0.05). For lower RT value, the global cognitive function and the performance in multiple cognitive domains were worse. ADL was significantly compromised in patients with AD having lower RT values (
< 0.05).
Lower RT value appear to be correlated with cognitive impairment, and RT may be an indicator of cognitive decline in patients with AD. Further studies are required to confirm our findings.
Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this ...property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20-2000 ng mL
with the limit of 0.79 ng mL
. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.
Two new tigliane- and daphnane-type diterpenoids, given the trivial names daphnegens A–B (1–2) were isolated from the buds of Daphne genkwa. Their structures were assigned on the basis of extensive ...spectroscopic. The absolute configurations of both compounds were determined by comparison of their calculated and experimental CD curves. In addition, compounds 1–2 were tested for their cytotoxic activities against MCF-7 and HepG-2 human cancer cell lines, and compound 2 showed remarkable cytotoxic activity against HepG-2 cell line with the IC50 value of 11.5 μM.
Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as ...heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
4 Clinical diagnosis and management of TIO are challenging because knowledge about this condition is still restricted to a few specialized centers, leading to delay in diagnosis and appropriate ...treatment. Decreased serum phosphate, tubular maximum reabsorption of phosphate/glomerular filtration rate, low or inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, and elevated alkaline phosphatase (ALP) accompanied with elevated FGF23 are typical laboratory findings. The therapeutic goal of conventional medical treatment is to alleviate clinical symptoms, increase the serum phosphate levels, normalize ALP, and maintain parathyroid hormone (PTH) in the normal range. Wei-Bo Xia, Department of Endocrinology, Key Laboratory of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, NHC, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China E-Mail: xiaweibo8301@163.com; Salvatore Minisola, Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome 00161, Italy E-Mail: salvatore.minisola@uniroma1.it; Jia-Jun Zhao, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China E-mail: jjzhao@sdu.edu.cn; Zhen-Lin Zhang, Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China E-mail: zhangzl@sjtu.edu.cn.
Thyroid nodules occur in about 60% of the population. A major challenge in thyroid nodule diagnosis is to distinguish between follicular adenoma (FA) and carcinoma (FTC). Here, we present a ...comprehensive thyroid spectral library covering five types of thyroid tissues. This library includes 121 960 peptides and 9941 protein groups. This spectral library can be used to quantify up to 7863 proteins from thyroid tissues, and can also be used to develop parallel reaction monitoring (PRM) assays for targeted protein quantification. Next, to stratify follicular thyroid tumours, we compared the proteomes of 24 FA and 22 FTC samples, and identified 204 differentially expressed proteins (DEPs). Our data suggest altered ferroptosis pathways in malignant follicular carcinoma. In all, 31 selected proteins effectively distinguished follicular tumours. Of those DEPs, nine proteins were further verified by PRM in an independent cohort of 18 FA and 19 FTC. Together, we present a comprehensive spectral library for DIA and targeted proteomics analysis of thyroid tissue specimens, and identified nine proteins that could potentially distinguish FA and FTC.
Here we present a comprehensive spectral library of 9941 protein groups for investigating the proteome of thyroid tissues. By using the spectral library and data‐independent acquisition (DIA) mass spectrometry, we identified nine differentially expressed proteins that could distinguish follicular thyroid adenoma from follicular thyroid carcinoma.
BACKGROUND Leukocyte telomere length (LTL) is regarded as a potential marker of biological aging. Oxidative stress plays a major role in the rate of telomeric DNA loss. The aim of this study was to ...explore whether the LTL was shorter in Chinese patients with premature coronary artery disease (PCAD) than in non-CAD controls and to determine the relationship between oxidative stress and LTL shortening in this population. MATERIAL AND METHODS Patients for coronary angiography were recruited. In total, 128 patients with PCAD and 128 non-CAD controls were enrolled. Samples of circulating leukocytes and plasma were collected. The mean LTL was measured using a polymerase chain reaction-based assay and expressed as the ratio of telomere repeat copies to single-copy gene (SCG) copies (T/S ratio). Reactive oxygen species (ROS) levels and total antioxidant capacity (T-AOC) were determined in plasma. RESULTS Both the T/S ratio (0.88±0.86 vs. 1.10±0.57, P=0.015) and telomere base pairs (4.97±1.37 kb vs. 5.32±0.91 kb, P=0.015) were significantly shorter in the PCAD group than in non-CAD controls. The T-AOC levels of the PCAD group were significantly lower than those of the non-CAD controls (0.482 mM 0.279, 0.603 mM) vs. 0.778 mM 0.421, 0.924 mM, P=0.000). The ratio of T-AOC to ROS in the PCAD patients was significantly decreased compared to that of the non-CAD controls (0.1026±0. 1587 Mm*ml/ng vs. 0.1435±0.1946 Mm*ml/ng, P=0.013). CONCLUSIONS The results point to a potential link between reduced LTLs in patients with PCAD and early onset of atherosclerosis. The decline in antioxidant capacity may play an important role in accelerating the attrition of telomeres in PCAD patients.
Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of ...this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients' clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15-0.60), 0.33 (0.17-0.65), and 0.19 (0.09-0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02-3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.
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