Comprehensive bioinformatics analysis of CYB561 expression in breast cancer:Link between prognosis and immune infiltration

Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship between CYB561 expression and immune infiltration in breast cancer remain unclear.Methods:The mRNA expression and clinical data of patients with breast cancer were obtained from The Cancer Genome Atlas database.Functional enrichment analysis was used to explore underlying biological functions associated with CYB561.The methylation status of CYB561 was analyzed using the MethSurv database.The enrichment score of immune cell infiltration for CYB561 in breast cancer was calculated using single-sample gene set enrichment analysis.The prognostic value of CYB561 was evaluated using Kaplan-Meier method and Cox regression analysis.Based on the results of the multivariate Cox analysis,a nomogram was constructed to predict the effect of CYB561 expression on overall survival(OS).Results:The results showed that CYB561 was highly expressed in breast cancer tissues.Hypomethylation of CYB561 is associated with an unfavorable prognosis.In multivariate Cox regression analysis,CYB561 was an independent prognostic factor for OS.Functional enrichment analysis indicated that estrogen signaling pathway,inflammatory response,KRAS signaling pathway,epithelial-mesenchymal transition,leukocyte migration,and regulation of lymphocyte activation were strongly enriched in the low CYB561 expression group.Additionally,CYB561 expression was negatively correlated with immune infiltration of B cells,plasmacytoid dendritic cells,dendritic cells,and neutrophils.Conclusion:CYB561 may serve as a potential biomarker for breast cancer diagnosis and prognosis.

同型半胱氨酸对FABP4启动子活性的影响

目的通过克隆脂肪酸结合蛋白4(FABP4)基因启动子,确定其活性核心区和功能片段,分析心血管疾病独立危险因子同型半胱氨酸(Hcy)对FABP4启动子活性的影响。方法应用生物信息学预测FABP4基因启动子区顺式转录作用元件和反式作用因子,以pGL3-Basic为载体,采用基因重组法构建启动子截取片段,转染HEK-293A细胞,观察不同截取片段的荧光素酶活性变化,确定活性最强的片段。进一步将核心启动子片段(-2000/-1)转染巨噬细胞,观察不同浓度Hcy和DNA甲基化抑制剂5-氮杂胞苷(AZC)对FABP4基因启动子活性的影响。结果不同长度截取片段转染HEK-293A细胞后检测荧光素酶活性结果显示,与pGL3对照组比较,-2000/-1片段转录活性最强。将核心启动子片段(-2000/-1)转染巨噬细胞并用不同浓度Hcy干预后,与0μmol/L Hcy组比较,100和200μmol/L Hcy组启动活性升高;与100μmol/L Hcy组比较,在100μmol/L Hcy基础上用AZC干预后,FABP4基因启动活性升高(P <0.05)。结论成功克隆FABP4启动子的4个片段,且确定FABP4基因核心启动子位于-2000/-1片段;Hcy可以促进FABP4基因核心启动子片段活性,补充AZC后可以进一步促进Hcy引起的FABP4启动子活性升高。

QTL mapping for grain number per spikelet in wheat using a high-density genetic map

Grain number per spikelet (GNS) is a key determinant of grain yield in wheat.A recombinant inbred line population comprising 300 lines was developed from a cross between a high GNS variety H461 and Chinese Spring from which the reference genome assembly of bread wheat was obtained.Both parents and the recombinant inbred lines were genotyped using the wheat 55K single nucleotide polymorphism(SNP) array.A high-density genetic map containing 21,197 SNPs was obtained.These markers covered each of the 21 chromosomes with a total linkage distance of 3792.71 c M.Locations of these markers in this linkage map were highly consistent with their physical locations in the genome assembly of Chinese Spring.The two parents and the whole RIL population were assessed for GNS in two consecutive years at two different locations.Based on multi-environment phenotype data and best liner unbiased prediction values,three quantitative trait loci (QTL) for GNS were identified.One of them located on chromosomes 2B and the other two on 2D.Phenotypic variation explained by these loci varied from 3.07%to26.57%.One of these QTL,QGns.sicau-2D-2,was identified in each of all trials conducted.Based on the best linear unbiased prediction values,this locus explained 19.59%–26.57%of phenotypic variation.A KASP(Kompetitive Allele-Specific PCR) marker closely linked with this locus was generated and used to validate the effects of this locus in three different genetic backgrounds.The identified QTL and the KASP marker developed for it will be highly valuable in fine-mapping the locus and in exploiting it for markerassisted selection in wheat breeding programs.

High expression of anti-apoptotic protein Bcl-2 is a good prognostic factor in colorectal cancer: Result of a metaanalysis

AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,Web of Science and EMBASE databases. Any eligible study must meet the following criteria:(1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry;(2) assessment of the relationships between bcl-2 expression and overall survival(OS),disease free survival(DFS),recurrent free survival(RFS) or clinic-pathological characteristics of CRC was included;(3) sufficient information was provided to estimate the hazard ratio(HR) or odds ratio and their 95% confidence intervals(CIs); and(4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTS A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS(pooled HR = 0.69,95%CI: 0.55-0.87,P = 0.002) and better DFS/RFS(pooled HR = 0.65,95%CI: 0.50-0.85,P = 0.001). Additionally,the subgroup analysis suggested that Bcl-2 overexpression was significantly associated withprognosis(OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally,our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage. CONCLUSION Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence,we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.

Seismogenic tectonics of the Qian-Gorlos earthquake in Jilin Province,China

The Qian-Gorlos earthquake, which occurred in the Songliao basin in Jilin Province in 1119 AD, was the largest earthquake to occur in NE China before the 1975 Haicheng earthquake. Based on historical records and surface geological investigations, it has been suggested previously that the earthquake epicenter was in the Longkeng area. However, other workers have considered the epicenter to be in the Halamaodu area based on the landslides and faults found in this region. No seismogenic structure has yet been found in either of these two regions.We tried to detect active faults in the urban areas of Songyuan City, where the historical earthquake was probably located. One of the aims of this work was to clarify the seismogenic structure so that the seismic risk in the city could be more accurately evaluated. The area was investigated and analyzed using information from remote sensing and topographic surveys, seismic data from petroleum exploration, shallow seismic profiles, exploratory geological trenches on fault outcrops, and borehole data. The geophysical data did not reveal any evidence of faults cutting through Cretaceous or later strata under the Longkeng scarp, which has been suggested to be structural evidence of the Qian-Gorlos earthquake. The continuous fault surfaces on the back edge of terraces in theHalamaodu area stretch for [3.5 km and were probably formed by tectonic activity. However, results from shallow seismic profiles showed that the faults did not extend downward, with the corresponding deep structure being identified as a gentle kink band. A new reverse fault was found to the west of the two suggested epicenters, which presented as a curvilinear fault extending to the west, and was formed by two groups of NE- and NW-trending faults intersecting the Gudian fault. Three-dimensional seismic and shallow seismic data from petroleum exploration revealed its distinct spatial distribution and showed that the fault may cut through Late Quaternary strata. Exploration boreholes and later geomorphological studies provided further proof of this. Based on these results and analysis,the Gudian fault was confirmed as having been an active fault since the Late Quaternary, with the possibility of earthquakes of magnitude [7 in the future. The QianGorlos earthquake was most probably the result of breakage on one or two sections of this 66-km-long fault.

Active faults and seismogenic models for the Urumqi city,Xinjiang Autonomous Region, China

We have studied the characteristics of the active faults and seismicity in the vicinity of Urumqi city, the capital of Xinjiang Autonomous Region, China, and have proposed a seismogenic model for the assessment of earthquake hazard in this area. Our work is based on an integrated analysis of data from investigations of active faults at the surface, deep seismic reflection soundings, seismic profiles from petroleum exploration, observations of temporal seismic stations, and the precise location of small earthquakes. We have made a comparative study of typical seismogenic structures in the frontal area of the North Tianshan Mountains, where Urumqi city is situated, and have revealed the primary features of the thrust-fold- nappe structure there. We suggest that Urumqi city is comprised two zones of seismotectonics which are inter- preted as thrust-nappe structures. The first is the thrust nappe of the North Tianshan Mountains in the west, con- sisting of the lower （root） thrust fault, middle detachment, and upper fold-uplift at the front. Faults active in the Pleistocene are present in the lower and upper parts of this structure, and the detachment in the middle spreads toward the north. In the future, M7 earthquakes may occur at the root thrust fault, while the seismic risk of frontal fold-uplift at the front will not exceed M6.5. The second structure is the western flank of the arc-like Bogda nappe in the east, which is also comprised a root thrust fault, middle detachment, and upper fold-uplift at the front, of which the nappe stretches toward the north; several active faults are also developed in it. The fault active in the Holocene is called the South Fukang fault. It is not in the urban area of Urumqi city. The other three faults are located in the urban area and were active in the late Pleistocene. In these cases, this section of the nappe structure near the city has an earthquake risk of M6.5-7, An earthquake Ms6.6, 60 km east to Urumqi city occurred along the structure in 1965.

Mapping a stable adult-plant stripe rust resistance QTL on chromosome 6AL in Chinese wheat landrace Yibinzhuermai

Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is one of the most important diseases threatening the yield and stability of wheat production in China and many other countries.Identification and utilization of new genes for durable stripe rust resistance are important for ongoing control of this disease.The objectives of this study were to identify quantitative trait loci(QTL)associated with adult-plant stripe rust resistance in the Chinese wheat landrace Yibinzhuermai(YBZR)and to provide wheat breeders with new sources of potentially durable resistance.A total of 117 recombinant inbred lines(RILs)(F5:8)derived from a cross between YBZR and highly susceptible cultivar Taichung 29(TC29)were assessed for stripe rust severity in field experiments at Wenjiang in 2016 and 2017 and Chongzhou in 2016,2017,2018,and 2019 in Sichuan following inoculation with a mixture of current Pst races.The RILs were genotyped using the Wheat55K single nucleotide polymorphism(SNP)array.Three QTL were identified on chromosome arms 6AL,5BL and 7DS.QYr.YBZR-6AL and QYr.YBZR-7DS conferred major effects in all field environments,explaining 10.6%to 14.7%and 11.5%to 21.2%of phenotypic variation,respectively.The QTL on 5BL and 7DS likely correspond to previously known QTL,whereas QYr.YBZR-6AL is probably novel.Haplotype analysis revealed that the resistance allele at QYr.YBZR-6AL was present in 2.8%of 324 Chinese wheat landraces.SNP markers closely linked with QYr.YBZR-6AL were converted to kompetitive allele-specific PCR markers and validated in the RIL population and a subset of 92 wheat cultivars.QYr.YBZR-6AL and its markers should be useful in breeding programs to improve the level and durability of stripe rust resistance.

A Pilot Survey of Mercury in Drugs, Cosmetics and Household Products Using Reliable Analytical Methods

The concentration of mercury (Hg) was accurately determined in more than 228 drugs, cosmetics and household products manufactured in a variety of countries. Some drugs were found to contain up to 4424 ppb Hg, and some skin creams contained up to 2769 ppm Hg. Hg in skin creams was found to be almost 100% elemental Hg (Hg0), a volatile species of Hg. Hg0 can enter the human body through inhalation and skin absorption, potentially resulting in the serious consequence of mercury poisoning. The mercury can also volatilize, contaminating the surrounding air. Other people, for example, infants and children, who are close to or contacting the skin of the person using the cosmetics, can also absorb the mercury. Total mercury (THg) was determined by combustion/trap/CVAFS. Methyl mercury (MeHg) and inorganic mercury (Hg2+) were determined by the ethylation based method. The emission of Hg0 was determined by evaporation/trap/CVAFS. All analyses were performed in accordance with explicit quality assurance and quality control protocols and procedures.

A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose APE.Thereafter,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart failure.Among eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinical assessment strategies,the RF model achieved better diagnostic efficacy and accuracy.Therefore,the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma

The important role of immunogenic cell death(ICD)in many tumors is increasingly being discovered.However,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well studied.We obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 study.We used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.

纤维素性纵隔炎的影像诊断

纤维素性纵隔炎是一种纵隔良性疾病, 是由纵隔中纤维组织增生引起。根据受累范围, 分为肉芽肿性和非肉芽肿性两种亚型。肉芽肿性通常与感染引起的异常免疫反应有关;非肉芽肿性可能是特发性的, 或与自身免疫有关。这两种亚型均会出现与重要纵隔结构梗阻或压迫相关的体征和症状。CT增强是诊断和鉴别诊断纤维素性纵隔炎的首选检查方法。影像学特征包括纵隔软组织浸润(伴或不伴钙化), 伴有纵隔血管结构和/或呼吸消化道的压迫或阻塞。当在适当的临床背景下发现这些特征时, 放射科医师就可以提出纤维素性纵隔炎的诊断。在初始和后续的影像学检查中, 仔细评估对于排除潜在恶性肿瘤、评估疾病进展、识别并发症和评估治疗反应至关重要。

Fine mapping and characterization of stripe rust resistance gene YrAYH in near-isogenic lines derived from a cross involving wheat landrace Anyuehong

Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.

基于自由体积理论的沥青分子模型黏度预测

沥青的黏度特性由化学结构决定.然而,目前在分子层面上对沥青动态黏度机理的认识并不清晰.本文采用分子动力学(molecular dynamic,MD)模拟,从自由体积的角度研究了沥青的黏度.基于一定范德瓦耳斯(van der Waals,vdW)半径下的自由体积预测,计算得到了沥青模型黏度与温度之间的关系.结果表明,沥青的动态黏度与自由体积有关;沥青模型的自由体积随vdW半径、沥青模型类型等参数变化,随vdW半径的减小而增大;单组分模型的自由体积明显大于多组分模型.利用不同半径的自由体积对沥青的动态黏度进行了预测,当vdW半径为1.39?时计算出来的自由体积预测的沥青模型黏度平均偏差最低.此外,不同沥青模型的平均偏差不同,四组分模型的平均偏差最小.黏度测试结论与模拟结果吻合较好,说明MD结果是可靠的.本文有助于理解沥青黏度的微观机理及其与分子结构间的关系.