Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

The Shaping of Woman's Language and Its Therapeutic Function through Images in "The Yellow Wallpaper"

In Perkins' "The Yellow Wallpaper",the wallpaper acts as woman's language.Through this interaction between the wallpaper and the heroine in in this story,Gilman displays to us women's embarrassing status in family and society,and leaves the reader to think of woman's future.

Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

Ureteral Ewing’s sarcoma in an elderly woman: A case report

BACKGROUND Ewing’s sarcoma(ES)is regarded as a skeletal tumor,with few instances of extraskeletal ES.A primary ES in the ureter is extremely rare.CASE SUMMARY We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter.Pathology of the excised mass indicated ES.The clinical treatment and pathologic characteristics in this case,and a review of the literature describing ES in the urinary system,are presented.CONCLUSION Due to the rarity and malignancy of ES in ureter,early diagnosis and prompt surgical treatment are critical.

Acid‐promoted Ir‐La‐S/AC‐catalyzed methanol carbonylation on single atomic active sites

Highly active Ir‐La‐S/AC catalyst was successfully prepared by co‐impregnation of an activated carbon（AC） carrier with a sulfuric acid solution of Ir and La species and compared with a tradition‐ally prepared Ir‐La/AC catalyst. High angle annular dark‐field‐scanning transmission electron mi‐croscopy（HAADF‐STEM） measurement results show that most of the Ir species on Ir‐La‐S/AC exist as single atomic sites, while those on Ir‐La/AC exist as nanoparticles with an average diameter of 1.5 nm. Evaluation of Ir‐La‐S/AC as a catalyst for heterogeneous carbonylation of methanol to acetyl gave a maximum TOF （turn‐over‐frequency） of 2760 h^–1, which was distinctly higher than that achieved by the Ir‐La/AC catalyst（approximately 1000 h^-1）. Temperature‐programmed desorption of ammonia（NH3‐TPD） result shows that the addition of sulfuric acid during the preparation pro‐cedure results in significantly more acidic sites on Ir‐La‐S/AC than those on Ir‐La/AC, which plays a key role in the enhancement of CO insertion as the rate‐determining step. Tempera‐ture‐programmed reduction（TPR） and in situ X‐ray photoelectron spectroscopy reveal that Ir spe‐cies are more reducible, and that more Ir^＋ might be formed by activation of Ir‐La‐S/AC than those on the Ir‐La/AC catalyst, which is thought to be beneficial for reductive elimination of AcI from Ir^3＋ species as an essential step for CH3I regeneration and acetyl formation.

Effects of loading rate and peak load on nanoindentation creep behavior of DD407 Ni-base single crystal superalloy

Nanoindentation experiments were conducted under loading rates of 500–6000μN/s and applied peak loads of 4000-12000μN to measure the creep behavior of DD407 Ni-base single crystal superalloy at room temperature.Experimental results demonstrated that DD407 Ni-base single crystal superalloy had a good creep resistance,but its creep properties were sensitive to the loading rate and peak load.The fitting creep parameters significantly increased with increasing loading rate and peak load based on the Findley’s model,and the corresponding creep mechanism was governed by dislocation based on the calculation of creep stress exponent.During nanoindentation creep tests,it was found that the hardness and reduced modulus decreased with increasing the loading rate and peak load,and through a dimensionless analysis,it was also noted that the effect of the dimensionless loading rate was stronger than that of dimensionless peak load on the creep properties.

Feminism, Patriarchy and Culture Dominance ——A review to "The Woman Warrior

The Woman Warrior" is an influential book in the 20th century making a thunder of voice in the world to accuse the stereotype of patriarchy and racism, which also shows the Chinese Americans’ difficulty of being edged to the cultural cliff. This article analyses the content and the style of the novel to see inside what the writer wants to express and to figure out the real reason of the inequality between sexes and reveal the truth of the western culture dominance. Feminism, Patriarchy and culture are the main factors considered in the article.

Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn’s disease

BACKGROUND Crohn’s disease(CD)is characterized by a multifactorial etiology and a significant impact of genetic traits.While NOD2 mutations represent well established risk factors of CD,the role of other genes is incompletely understood.AIM To challenge the hypothesis that single nucleotide polymorphisms(SNPs)in the genes CLEC5 A and CLEC7 A,two members of the C-type lectin domain family of pattern recognition receptors,may be associated with CD.METHODS SNPs in CLEC5 A,CLEC7 A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays.Therefore,DNA samples from 175 patients and 157 healthy donors were employed.Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses.RESULTS In accordance with previous studies,rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD(allelic P values=0.0368 and 0.0474,respectively).Intriguingly,for genotype AA of rs1285933 in CLEC5 A,a potential association with CD(recessive P=0.0523;odds ratio=1.90)was observed.There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7 A.Variants of rs1285933 had no impact on CLEC5 A gene expression.In contrast,genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed.There is no statistical interactionbetween the tested SNPs of NOD2 and CLEC5 A,suggesting of a novel pathway contributing to the disease.CONCLUSION Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5 A with CD.The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.

Semiconducting single-walled carbon nanotubes synthesized by S-doping

An approach was presented for synthesis of semiconducting single-walled carbon nanotubes(SWNTs) by sulfur(S) doping with the method of graphite arc discharge. Raman spectroscopy, UV-vis-NIR absorption spectroscopy and electronic properties measurements indicated the semconducting properties of the SWNTs samples. Simulant calculation indicated that S doping could induce convertion of metallic SWNTs into semiconducting ones. This strategy may pave a way for the direct synthesis of pure semiconducting SWNTs.

Three-dimensional stereotactic surface projection in the statistical analysis of single photon emission computed tomography data for distinguishing between Alzheimer's disease and depression

AIM To evaluate usefulness of single photon emission computed tomography(SPECT) with three-dimensional stereotactic surface projection(3D-SSP) in distinguishing between Alzheimer's disease(AD) and depression.METHODS We studied 43 patients who presented with both depressive symptoms and memory disturbance. Each subject was evaluated using the following:(1) the Minimal Mental State Examination;(2) the Hamilton Rating Scale for Depression;(3) Clinical Global Impression-Severity scale(CGI-S); and(4) SPECT imaging with 3D-SSP.RESULTS The MMSE scores correlated significantly with the maximum Z-scores of AD-associated regions. CGI-S scores correlated significantly with the maximum Z-scores of depression-associated regions. Factor analysis identified three significant factors. Of these, Factor 1 could be interpreted as favouring a tendency for AD, Factor 2 as favouring a tendency for pseudo-dementia, and Factor 3 as favouring a depressive tendency.CONCLUSION We investigated whether these patients could be categorized as types: Type A(true AD), Type B(pseudodementia), Type C(occult AD), and Type D(true depression). The factor scores in factor analysis supported the validity of this classification. Our results suggest that SPECT with 3D-SSP is highly useful for distinguishing between depression and depressed mood in the early stage of AD.

Application of single-cell omics in inflammatory bowel disease

Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.Single-cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as single-cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through single-cell omics can change our approach to translational research.As novel techniques evolve through multiplexing single-cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.

A single nucleotide polymorphism in the IL1RL1 gene is associated with Behcet's disease in a Chinese Han population

AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.

Modeling and Analysis of Single Machine Scheduling Based on Noncooperative Game Theory

Considering the independent optimization requirement for each demander of modernmanufacture, we explore the application of noncooperative game in production scheduling research,and model scheduling problem as competition of machine resources among a group of selfish jobs.Each job has its own performance objective. For the single machine, multi-jobs and non-preemptivescheduling problem, a noncooperative game model is established. Based on the model, many prob-lems about Nash equilibrium solution, such as the existence, quantity, properties of solution space,performance of solution and algorithm are discussed. The results are tested by numerical example.

Fluorescence-based Multiplex PCR-Single Strand Conformation Polymorphism (SSCP) Analysis of 16S Ribosomal DNA Using Capillary Electrophoresis

The rRNA genetic locus is found in all prokaryotic organisms, and is highly conservative, although its relatively stable variations are found frequently in different bacteria. The utility of this locus as a taxonomic and phylogenetic tool has been reported widely. This study, aimed at 16S rRNA gene (16S rDNA) and with the help of biomolecular methods, attempted to achieve the goal of rapid identification of common pathogens. In this study, 333 clinical isolated pathogenic bacteria were collected. Two pairs of primers were chosen and labeled with different fluorescent dyes and then used to amplify the genomic DNA extracted from bacteria. The PCR products were then detected by capillary electrophoresis-single strand conformation polymorphism (CE-SSCP). In order to pursue higher resolution and peak-separation effect, a high efficient separating medium, liner polyacrylamidedel (LPA), was put to use in this study. Finally, every bacteria colony generated distinct patterns from each other, which were easily to be used for identification. These results indicated that PCR-CE-SSCP was a rapid identification method for bacterial identification, with the aspects of high efficiency and high precision. Compared with traditional method, this technology is of great utility for clinical use especially for its high sensitivity.

Y Specific Sequence Gene Analysis of Single Fetal Nucleated Erythroblasts from the Peripheral Blood of Pregnant Women

The single cell isolation technique was used to detect fetal nucleated erythroblasts at a single cell level from the peripheral blood of pregnant women in order to investigate the feasibility of this method for noninvasive prenatal diagnosis. Single fetal nucleated erythroblasts were isolated from the peripheral blood samples from 51 pregnant women by micromanipulation techniques after density gradient centrifugation. Nested polymerase chain reaction method was used to amplify the SRY gene. It was found that the concordance rate of amplification results with real fetal sex was 82.61 %. The sensitivity and specificity were 80 % and 87.50 % respectively. It was suggested that it is feasible and promising in non invasive prenatal diagnosis to detect fetal nucleated erythroblasts at a single cell level by using micromanipulation techniques.

MORPHOLOGY OF(Mn,Fe)S SINGLE CRYSTAL GROWTH IN CAST STEEL

The step pattern of single crystal growth and the morphology at equilibrium state of(Mn, Fe)S on the wall of micro-voids in ZG25 cast steel have been observed using scanning electron microscope.The face-centred cubic(Mn,Fe)S single crystal at equilibrium state is shown to be tetrakaidecahedron consisted of eight{111}planes and six{100}planes,and is a typical example of the O_h—m3m cubic crystal system.

神经肽S受体基因多态性与原发性失眠的相关性研究

目的探讨神经肽S受体(neuropeptide S receptor,NPSR)基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs323917、rs323920、rs323922、rs2530547、rs324957)与原发性失眠(primary insomnia,PI)的相关性。方法选取2016年12月至2019年5月在甘肃省人民医院睡眠医学中心门诊就诊并确诊的PI患者157例作为PI组,选取同期133名健康体检者作为对照组。抽取受试者的静脉血标本,并提取DNA、聚合酶链反应(polymerase chain reaction,PCR)扩增、琼脂糖凝胶电泳,目标位点测序对rs323917、rs323920、rs323922、rs2530547、rs324957单核苷酸位点进行基因分型,同时行标准多导睡眠监测,分析基因多态性与PI的相关性。结果两组受试者的NPSR SNP位点(rs323917、rs323920、rs323922、rs2530547)基因型分布和等位基因频率及rs324957等位基因频率的差异均无统计学意义(P>0.05);rs324957位点基因型分布差异有统计学意义(P=0.034);两组受试者不同单倍型频率差异无统计学意义(P>0.05)。结论NPSR rs324957 SNP位点基因型表达或与PI相关,且以AG基因型为主。

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Improved data analysis method of single-molecule experiments based on probability optimization

To extract the dynamic parameters from single molecule manipulation experiments, usually lots of data at different forces need to be recorded. But the measuring time of a single molecule is limited due to breakage of the tether or degradation of the molecule. Here we propose a data analysis method based on probability maximizalion of the recorded time trace to extract the dynamic parameters from a single measurement. The feasibility of this method was verified by dealing with the simulation data of a two-state system. We also applied this method to estimate the parameters of DNA hairpin folding and unfolding dynamics measured by a magnetic tweezers experiment.