Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV.METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV.RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA Ⅰ/Ⅱ restricted recognition epitopes reported by some investigators.CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients

AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes.METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed.RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ2 = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ2 = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively.CONCLUSION: HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function.

Construction of Land Resource Security System for Core Grain Production Region in Henan Province

To solve the contradiction between supply and demand of land, the con- struction of land resource security guarantee system is an important part to coordi- nate the economic development and cultivated land protection in the core grain pro- duction region. Based on the deep analysis on the land resources characteristics and problems using the combined method of literature review method with qualita- tive and quantitative analysis, we constructed the land resource security system for different categories according to the land use principles of optimization, intensivism, improvement, and overall planning, and proposed the corresponding supporting mea- sures. The results showed that controlling the new increase, promoting the reclama- tion and improvement of land are the basis for land resource security, clearing the idle, improving the utilization rate of stock are the core of the efficient use of land resources, and establishing a unified urban and rural construction land market is the key to promoting the economical and intensive utilization of land resources, provid- ing scientific basis for the sustainable utilization of land resources in the core grain production regions.

Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning

Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis.The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance,interpretability,and generalizability.Specifically,we argue that a core set of co-altered brain regions(namely‘core regions’)comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients.Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain.We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.

STRUCTURE IN THE PRECORE REGION OF HEPATITIS B CORE GENE AFFECTING ITS EXPRESSION IN E.coil

Restriction fragments of HBV-DNA, cleaved by endonuclease HhaI,containing HBcAg gene were trimmed by BAL-31 exonuclease to remove different lengths of the precore sequence.They were inserted into plasmid pUR222 at EcoRI site through synthetic linker ligation. Transformants in E.coli BMH7118 showing different levels of HBcAg gene expression were screened and analyzed for their nucleotide sequences in the junction region both by Maxam and Gilbert's chemical degradation method and by M13 chain termination method. Results of sequence analysis of different transformants revealed a partial palindromic (loop and stem) structure, at -7 to -35 nucleotide with regard to ATG of the HBcAg gene as position +1, which has dramatic effect on the level of expression of the inserted gene using the same promoter,SD sequence and identical N-terminus.The amount of HBcAg synthesized differed from 9% in the high expressing plasmid to less than 0.01% of the total cell proteins in the low expressing transformants.The findings were compared to results obtained by other workers in studies of HBcAg expression in procaryotes and their significance in the expression of eucaryotic genes in procaryotic cells were discussed.

Constructing a Core Collection for Maize (Zea mays L.) Landrace from Wuling Mountain Region in China

Based on the genetic clustering from 42 microsatellite （SSR） markers with a combination of their geographic origin and germplasm characteristics, 124 maize landraces from Wuling Mountain region in China were used for constructing a core collection. Four evaluating parameters for maize landrace core collection, including mean difference percentage （MD）, variance difference percentage （VD）, coincidence rate of range （CR）, and variable rate of coefficient of variation （VR）, were assessed With 20 quantitative traits. It was shown that genetic relationships among landraces in Wuling Mountain region had the tendency to associate with their geographic origins. The 124 landraces were clustered into 18 subgroups when the coefficient of genetic similarity （GS） is 0.28. Eighteen landraces, each of which was from one subgroup, were applied to construct the core collection with a sampling percentage of 15%. Comparison of the initial and core collection indicated that there existed no significant differences in most quantitative traits. An average of 6.3 and 6.5 alleles were detected in the initial and core collection, respectively. Mean polymorphism information content in the core collection （0.75） was higher than that in the initial one （0.72）. MD was lesser than 20% and CR was more than 80%. The results showed that the sampling strategy would be feasible for constructing the core collection that well represents the genetic diversity of the initial one.

THE LABORATORY OF ICE CORE AND COLD REGIONS ENVIRONMENT

Affiliation unit: Lanzhou Institute of Glaciology and Cold Regions Environment, CAS Brief history: The Laboratory of Ice Core and Cold Regions Environment (LICCRE) was formally approved to open domestically and internationally by Chinese Academy of Sciences in April 1997. It is attached to the Lanzhou Institute of Glaciology and Geocryology, CAS.

儿童与成人慢性乙型肝炎患者乙型肝炎病毒Core基因区准种特征及正选择压力差异分析

儿童与成人慢性乙型肝炎患者的临床特征差异明显。乙型肝炎病毒(Hepatitis B virus,HBV)病毒准种特征与其致病特性紧密相连,HBV病毒Core基因区富含免疫表位,该区域的准种特征直接反映病毒变异与病毒应对宿主免疫压力间的动态过程。文章通过扩增170名儿童慢性乙型肝炎患者及121名成人慢性乙型肝炎患者病毒Core基因区,按照病毒基因型以及病毒e抗原(Hepatitis B virus e antigen,HBe Ag)状态进行分组,使用序列复杂度、多样性、非同义突变率(Non-synonymous substitution ratio,d N)、同义突变率(Synonymous substitution ratios,d S)等指标衡量不同组别之间的病毒准种特征;使用不同模型计算不同组别中受到正选择压力的位点,进一步结合HBV Core基因区免疫表位信息,进行正选择位点的定位分析。结果发现,儿童乙型肝炎病毒患者体内病毒Core基因区序列复杂性和多样性低于成人患者,且前者Core基因区正选择位点个数显著低于后者,这说明儿童慢性乙型肝炎患者体内病毒受到的选择压力低于成人患者。在儿童及成人慢性感染病人组中,HBe Ag阳性病人体内病毒受到的选择压力低于HBe Ag阴性病人。儿童及成人慢性感染患者体内病毒存在13个正选择位点,大多数正选择位点位于已知的抗原表位上。本研究从分子进化角度揭示了儿童与成人慢性乙型肝炎病例体内病毒Core基因区序列准种差异,为两类病人显著不同的临床表征提供了群体遗传学的解释。

Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity

Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.

瘤周水肿区与肿瘤核心区体积比值对脑胶质瘤的诊断与预后评估价值

目的探讨MRI中瘤周水肿区与肿瘤核心区体积比值(VPE/VTC)这一新指标在脑胶质瘤诊断与预后评估中应用价值。方法回顾性分析了新疆医科大学第二附属医院2019年1月~2023年6月收治的51例脑胶质瘤患者的术前MRI影像数据及临床资料,包括22例低级别胶质瘤(LGG)和29例高级别胶质瘤(HGG)。利用3D-Slicer软件对通过不同MRI序列配准后半自动勾画肿瘤核心区与瘤周水肿区,并手动调整确保准确性。构建核心区和水肿区的三维模型并进行定量分析,计算VPE/VTC比值。结果HGG组VPE/VTC比值高于LGG组(P<0.05)。VPE/VTC比值在区分HGG与LGG中具有较高的诊断效能(AUC=0.851),最佳截断点为0.929,Youden指数达到最高值0.771,敏感度为86.2%,特异度为90.9%。Kaplan-Meier生存分析显示,VPE/VTC比值较高的患者预后较差(P<0.05),在预后评估中表现出良好的预测能力。结论VPE/VTC比值作为一种新颖的评估指标,具有重要的临床应用价值,能够为脑胶质瘤患者个性化治疗和手术方案提供更有效的支持。

区域双核结构对城市群科技创新的影响——基于空间杜宾模型的实证分析

城市群的核心优势及功能之一是科技创新,而区域双核结构对城市群的科技创新具有重要影响。基于区域双核结构理论,分别测算了我国19个城市群的中心性和门户性指标并进行聚类分析,发现长三角、京津冀等8个城市群为双核结构,哈长、中原等11个城市群为单核结构。采用空间杜宾模型进一步实证分析发现,区域双核结构显著促进了城市群科技创新水平,并且对南方地区、西部地区以及单一省份组成的城市群的科技创新具有更明显的促进作用。各城市群应注重发挥核心城市对周边科技创新的带动作用促进协调发展;具备双核结构特征的城市群可以充分发挥中心城市数量及空间分布优势,带动城市群发展及科技创新。

“双城记”:京津冀区域双核结构的实证分析

在京津冀协同发展快速推进的大背景下,进一步理清京津两个核心城市的辐射带动作用对于唱好“双城记”具有重要意义。基于区域双核结构理论,通过测算国内19个城市群的中心性和门户性指标并进行聚类分析,可以发现京津冀与其中7个城市群为双核结构;进而借助引力模型和场强模型,探讨京津冀区域内所有可能的双核结构组合,确定“北京-天津”是京津冀城市群内影响最大且最为稳定的双核结构,其中北京为中心城市,天津为门户城市。进一步分析不难发现,2019年之后京津双核结构的作用正在弱化,其在京津冀城市群内的功能有待进一步明确及发挥,尤其是天津如何进一步发挥其港口及门户城市的作用有待进一步探讨。

区域高职教育核心竞争力的布局落点与发展策略——基于广东省高职院校高水平专业群的分析

立足区域高职教育核心竞争力发展的现实需求,着眼广东省现有国家、省级高水平专业群建设的整体情况与结构,形成对广东省高职教育核心竞争力布局落点的基本描绘。对高水平专业群组群逻辑主线进行归纳提炼,提出技术演进多元化、区域优势产业特色化、院校专业发展类属化三种类型的组群走向,并进行内部细化区分。在此基础上,从专业群聚集化发展、校企协同治理机制建设、特色优势专业群打造等维度提出提升区域高职教育核心竞争力的路径。

云地闪电通道的径向结构及光辐射特征

为揭示云地闪电通道形成和发展过程的微观物理机制,研究了云地闪电通道的径向结构及光辐射特征。利用无狭缝高速摄谱仪,在青海高原地区实施野外观测试验。在一次云地闪电中记录到了清晰可见的通道核心,而且在通道核心的外边缘和外部发光通道之间发现一个较弱的发光区。基于光谱观测结果,对比分析了首次回击和第三次继后回击的光辐射特征。实验验证了闪电通道电晕鞘模型,确定了连接点的位置,估算得到两个回击的闪击距离分别为57 m和53 m,并证实了回击放电最强的点在连接点处。由此可推断,在回击初期,云地闪电回击通道沿径向由内到外依次为通道核心-弱发光区-电晕鞘外层,即闪电通道内沿通道径向的电荷分布是不均匀的,闪电通道的光辐射特征与放电强度和持续时间密切相关。

我国省级地区数字经济核心产业规模及其差异演变

为了科学准确衡量我国省级地区数字经济规模和空间差异演变趋势,本文提出一种兼顾核算科学性和统计兼容性的方法,测算了2007—2020年我国30个省(区、市)的数字经济核心产业及其四类细分产业的增加值规模,进而分析了数字经济核心产业的空间发展格局和不平衡性的演变趋势,并通过SAR模型实证检验了我国数字经济核心产业发展的影响因素和空间溢出效应。研究显示:(1)30个省(区、市)的数字经济核心产业的总体规模差异显著。(2)四大类核心产业的空间发展格局呈现由东到西递减趋势;数字要素驱动业进一步向东部优势地区集聚,其他产业呈现从东部地区和东北地区向中西部地区转移的趋势。(3)各地区间的差异是造成我国数字经济差异的主要原因。(4)经济增长水平、政府科技支持力度、对外开放水平和技术创新水平与数字经济核心产业发展高度相关,这些因素的影响都存在空间溢出效应。

基于Mask R-CNN的锅炉火焰图像核心高温区域提取

为了提高锅炉火焰核心高温区域特征提取的准确性和稳定性,结合四角切圆燃烧锅炉火焰特点,提出了一种基于Mask R-CNN的火焰核心高温区域轮廓提取方法。通过某330 MW燃煤锅炉工业火焰监控系统获取约10 000帧历史运行工况的火焰图像进行建模,并对升负荷工况的火焰图像进行在线处理验证。结果表明:基于Mask R-CNN模型的核心高温区域检测精准率达到92.35%,相比于传统的阈值分割法、边缘检测法具有更高的稳定性;Mask R-CNN模型能更好地适应变负荷时脉动火焰波动、快速变化的特点,轮廓边缘受其他区域的影响较小,有助于针对火焰核心高温区域轮廓进行火焰几何特征、分布特征的提取计算。

我国本土气温指数期货产品的研发设计——源于京津冀“首都经济圈”核心功能区的气温数据

我国幅员辽阔,对天气变化非常敏感,迫切需要对天气风险进行有效管理,以消除或减少天气风险对各行业的不利影响。从产品研发设计视角出发,以京津冀“首都经济圈”核心功能区为例,参考国外成熟产品,对我国本土气温指数期货产品进行合约设计和模拟定价,根据行业需求阐述产品的应用价值,提出产品在天气风险管理中的显著作用。研究贡献有,搭建起我国本土气温指数期货产品的研发体系;基于国外成熟市场规则构建出符合我国国情的气温指数期货产品标准化合约框架;运用ARMA模型构建出精确度高的气温预测模型;采用蒙特卡罗模拟法制定出气温指数期货两款产品价格;明确产品的应用推广需求和风险管理作用。

Experimental investigation on pyrolysis products and pore structure characteristics of organic-rich shale heated by supercritical carbon dioxide

The efficient pyrolysis and conversion of organic matter in organic-rich shale,as well as the effective recovery of pyrolysis shale oil and gas,play a vital role in alleviating energy pressure.The state of carbon dioxide(CO_(2))in the pyrolysis environment of shale reservoirs is the supercritical state.Its unique supercritical fluid properties not only effectively heat organic matter,displace pyrolysis products and change shale pore structure,but also achieve carbon storage to a certain extent.Shale samples were made into powder and three sizes of cores,and nitrogen(N_(2))and supercritical carbon dioxide(ScCO_(2))pyrolysis experiments were performed at different final pyrolysis temperatures.The properties and mineral characteristics of the pyrolysis products were studied based on gas chromatography analysis,Xray diffraction tests,and mass spectrometry analysis.Besides,the pore structure characteristics at different regions of cores before and after pyrolysis were analyzed using N_(2) adsorption tests to clarify the impact of fracturing degree on the pyrolysis effect.The results indicate that the optimal pyrolysis temperature of Longkou shale is about 430℃.Compared with N_(2),the oil yield of ScCO_(2) pyrolysis is higher.The pyrolysis oil obtained by ScCO_(2) extraction has more intermediate fractions and higher relative molecular weight.The ScCO_(2) can effectively improve the pore diameter of shale and its effect is better than that of N_(2).The micropores are produced in shale after pyrolysis,and the macropores only are generated in ScCO_(2) pyrolysis environments with temperatures greater than 430℃.The pore structure has different development characteristics at different pyrolysis temperatures,which are mainly affected by the pressure holding of volatile matter and products blocking.Compared to the surface of the core,the pore development effect inside the core is better.With the decrease in core size,the pore diameter,specific surface area,and pore volume of cores all increase after pyrolysis.

中国西南地区中世纪暖期以来的温湿模式:来自黔西高原野鸡坪泥炭沉积记录的证据

通过高密度AMS14C测年构建黔西高原野鸡坪泥炭YJP01钻孔的年代框架,基于多环境代用指标分析,并结合多元统计分析,探究野鸡坪泥炭中主要地球化学元素来源及其环境指示意义,恢复该区中世纪暖期至小冰期详细的气候变化过程。结合已有研究成果,解析西南地区及临近区域在这2个时期气候条件的空间格局及其影响因素。结果表明:①野鸡坪地区中世纪暖期(1 200―1450年)和小冰期(1 450―1880年)的气候特征分别为暖湿和冷干,与周边地区的古气候记录具有较好的一致性;②西南地区在这2个气候特征时期存在“暖湿-冷干”和“暖干-冷湿”2种温湿度组合模式,在空间上存在一条分界线并呈现东西分异模式;③西风南支位置的南北移动对西南地区过去千年的温湿度组合模式具有明显影响。