原子精度制造新原理和新方法

目前航空航天、核物理、微电子、光电子和半导体等国家战略领域高性能装备的性能需求日渐严苛,核心零部件的制造精度必须迈进原子级水平,亟需研究原子精度的高性能制造新原理和新方法。本文归纳并提出了目前迫切需求的原子级表面精度、原子级结构精度、原子级损伤控制以及原子级特征尺寸结构创成四大原子精度制造核心能力,从能场辅助原子级切削、多能场辅助原子有序排布、表面能弱化原子精度材料去除以及超光学衍射极限的原子精度制造四大方向进行系统梳理,介绍了面向不同应用场景的原子精度制造新原理和新方法的研究现状,并概述了各类方法的优势和缺点,从中提炼出多能场耦合条件下的能量和原子间相互作用机理这一关键科学问题,并从四大方向上对未来我国原子级制造的基础研究提出了建议。

Field-assisted machining of difficult-to-machine materials

Difficult-to-machine materials (DMMs) are extensively applied in critical fields such as aviation,semiconductor,biomedicine,and other key fields due to their excellent material properties.However,traditional machining technologies often struggle to achieve ultra-precision with DMMs resulting from poor surface quality and low processing efficiency.In recent years,field-assisted machining (FAM) technology has emerged as a new generation of machining technology based on innovative principles such as laser heating,tool vibration,magnetic magnetization,and plasma modification,providing a new solution for improving the machinability of DMMs.This technology not only addresses these limitations of traditional machining methods,but also has become a hot topic of research in the domain of ultra-precision machining of DMMs.Many new methods and principles have been introduced and investigated one after another,yet few studies have presented a comprehensive analysis and summarization.To fill this gap and understand the development trend of FAM,this study provides an important overview of FAM,covering different assisted machining methods,application effects,mechanism analysis,and equipment design.The current deficiencies and future challenges of FAM are summarized to lay the foundation for the further development of multi-field hybrid assisted and intelligent FAM technologies.

The Xu＇s chart for prostate biopsy： a visual presentation of the added value of biomarkers to prostate-specific antigen for estimating detection rates of prostate cancer

Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below 30%, especially among patients with PSA levels at 4-10 ng ml-1. In the past several years, additional biomarkers, such as Prostate Health Index, PCA3 and genetic risk score （GRS） derived from multiple PCa risk-associated single nucleotide polymorphisms （SNPs） have been shown to provide added value to PSA in discriminating prostate biopsy outcomes. However,

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort

Inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory disease of the digestive tract with increasing prevalence globally.Although venous thromboembolism(VTE)is a major complication in IBD patients,it is often underappreciated with limited tools for risk stratification.AIM To estimate the proportion of VTE among IBD patients and assess genetic risk factors(monogenic and polygenic)for VTE.METHODS Incident VTE was followed for 8465 IBD patients in the UK Biobank(UKB).The associations of VTE with F5 factor V leiden(FVL)mutation,F2 G20210A prothrombin gene mutation(PGM),and polygenic score(PGS003332)were tested using Cox hazards regression analysis,adjusting for age at IBD diagnosis,gender,and genetic background(top 10 principal components).The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve(AUC).RESULTS The overall proportion of incident VTE was 4.70%in IBD patients and was similar for CD(4.46%),UC(4.49%),and unclassified(6.42%),and comparable to that of cancer patients(4.66%)who are well-known at increased risk for VTE.Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers,hazard ratio(HR)was 1.94,95%confidence interval(CI):1.42-2.65.In contrast,patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores(middle 8 deciles),HR was 2.06(95%CI:1.57-2.71).The AUC for differentiating VTE diagnosis was 0.64(95%CI:0.61-0.67),0.68(95%CI:0.66-0.71),and 0.69(95%CI:0.66-0.71),respectively,for F5/F2 mutation carriers,PGS,and combined.CONCLUSION Similar to cancer patients,VTE complications are common in IBD patients.PGS provides more informative risk information than F5/F2 mutations(FVL and PGM)for personalized thromboprophylaxis.

Foundations and Applications of Information Systems Dynamics

Although numerous advances have been made in information technology in the past decades,there is still a lack of progress in information systems dynamics(ISD),owing to the lack of a mathematical foundation needed to describe information and the lack of an analytical framework to evaluate information systems.The value of ISD lies in its ability to guide the design,development,application,and evaluation of largescale information system-of-systems(So Ss),just as mechanical dynamics theories guide mechanical systems engineering.This paper reports on a breakthrough in these fundamental challenges by proposing a framework for information space,improving a mathematical theory for information measurement,and proposing a dynamic configuration model for information systems.In this way,it establishes a basic theoretical framework for ISD.The proposed theoretical methodologies have been successfully applied and verified in the Smart Court So Ss Engineering Project of China and have achieved significant improvements in the quality and efficiency of Chinese court informatization.The proposed ISD provides an innovative paradigm for the analysis,design,development,and evaluation of large-scale complex information systems,such as electronic government and smart cities.

Prostate cancer risk-associated genetic markers and their potential clinical utility

Prostate cancer （PCa） is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and Iow-penetrance PCa risk-associated single-nucleotide polymorphisms （SNPs） from genetic association studies in PCa cases and controls, especially those from genome-wide association studies （GWASs）. A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations.

Current progress and questions in germline genetics of prostate cancer

Dramatic progress has been made in the area of germline genetics of prostate cancer(PCa)in the past decade.Both common and rare genetic variants with effects on risk ranging from barely detectable to outright practice-changing have been identified.For men with high risk PCa,the application of genetic testing for inherited pathogenic mutations is becoming standard of care.A major question exists about which additional populations of men to test,as men at all risk levels can potentially benefit by knowing their unique genetic profile of germline susceptibility variants.This article will provide a brief overview of some current issues in understanding inherited susceptibility for PCa.

Efficient oxidative degradation of 2-chlorophenol and 4-chlorophenol over supported CuO-based catalysts

A series of metal oxide catalysts for catalytic oxidative degradation of 2-chlorophenol （2-CP） and 4-chlorophenol （4-CP） were prepared, and the supported CuO catalysts were studied particularly. The supported CuO catalysts were characterized by XRD and NH3-TPD techniques, in which CuO/γ-Al2O3 exhibited high degradation activity. The addition of Na2O or K2O into CuO/γ-Al2O3 improved the oxidative degradation of CPs remarkably, in which Na2O was more efficient than K2O. Over CuO/γ-Al2O3-Na2O, CPs were completely converted and the liberation of the inorganic chloride from 2-CP or 4-CP reached 97% or 100% respectively at 30 ？C for 2 h. The supported CuO catalysts with good dispersion of CuO particles and less acid sites were favorable for the efficient oxidative degradation of CPs. In addition, the initial pH of the reaction solution was found to be an important factor which influenced the catalytic oxidative degradation of CPs and the initial pH of 11.2 and 9.8 was preferred for the oxidative degradation of 2-CP and 4-CP respectively over CuO/γ-Al2O3 catalyst.

全基因组关联研究发现中国人群前列腺癌两个新易感位点9q31.2和19q13.4

0前言在全球范围内，前列腺癌的发病率和病死率存在着巨大差异。该病在西方发达国家发病率最高，在非裔美国人群病死率最高，而在亚洲人群中发病率及病死率均为全球最低，提示不同人种在前列腺癌的遗传方面存在异质性。在欧美和日本人群中，全基因组关联研究（GWAS）技术已经被用于检测前列腺癌的遗传易感性位点，但至今尚无关于GWAS检测中国人群前列腺癌易感位点的报道。

烟草细胞中高效表达提高血清半衰期的药用蛋白

小分子治疗蛋白，如干扰素α2b（IFNα2）和人生长激素（hGH），由于其对血清蛋白酶的易感性及分子小，可被肾迅速清除，因而一般在血清中的半衰期都很短。化学衍生处理虽可以克服这些问题，但却要以降低蛋白的生物活性为代价。本研究建立了一种新方法，使干扰素仅2b（IFNα2）和人类生长激素（hGH）在烟草细胞中高效表达为阿拉伯半乳糖聚糖糖蛋白嵌合体（AGP）。这样不仅提高了药用蛋白的产量，而且提高了其血清半表期。这种嵌合糖蛋白的分泌量比没有糖基化时高500～1800倍。重要的是，与未糖基化的干扰素和人生长激素相比，这种嵌合糖蛋白的体内血清半衰期提高13倍，生物活性仍保持与未糖基化时相似。这种嵌合糖蛋白注射到小鼠体内未引起免疫性反应。

Performance evaluation from stochastic statecharts representation of flexible reactive systems:a simulation approach

This paper focuses on the performance analysis of flexible reactive systems. The performance analysis consists of two phases： first system modeling, second performance evalua-tion. The paper models the flexible reactive system by the stochas-tic statecharts method, and uses the simulation method to evalu-ate the performance. To make use of the feature of event-triggered state transitions in the statecharts, a new method of simulation is proposed based on the techniques of the discrete-event system simulation. The new method solves the problem of computer imple-mentation of stochastic events, probabilistic transition, concurrent states, paral el actions, and broadcast communication mechanism in the stochastic statecharts. An example of a flexible manufactur-ing system is presented. The simulation result of the example is consistent with the analytical result, which shows the feasibility of the proposed new simulation method.

The Theoretically Studies and Field Testing of Self-Insulation Exterior Wall in the Hot Summer and Cold Winter Zone

The energy efficiency design of the exterior wall in the buildings of the hot summer and cold winter zone of China should consider the heat prevention in summer and the heat insulation in winter. The self-insulation of the exterior?wall is a more feasible design to satisfy the energy efficiency of buildings in the?zone. However, the systematic research is urgently needed for the self-insulation of the exterior wall in the hot summer and cold winter zone of China. The paper tested the thermal performance of the common non-clay materials such as shale sintered hollow brick, sand autoclaved aerated concrete block, etc. by means of indoor experiments. The energy efficiency effect of the common materials was verified using dynamic calculation soft PKPM and several constitutions of exterior wall with different main bricks and insulation materials on the heat bridge were simulated, too. Besides, the tests of the thermal performance of exterior wall in real constructions were carried out to testify the practical effect of the recommended constitutions of exterior wall with different main bricks and insulation materials on the heat bridge. The conclusions are: the physical and thermal properties of the six non-clay wall material are better than the clay porous brick;the thermal performance of the non-clay brick can be improved obviously through the rational arrangement of the holes;shale sintered hollow brick after increasing the holes and rationalizing the hole arrangement and sand autoclaved aerated concrete block are recommended for buildings in the hot summer and cold winter area of China. The dynamic calculation results show that the thermal performances?of the non-clay materials are all satisfied with the energy efficiency;The heat transfer coefficient of the exterior wall with composition?③,?in which?the main wall was sand autoclaved aerated concrete block and the material on the heat bridge was sand autoclaved aerated concrete plate, is the smallest among the three recommended compositions.

Research on Criminal Legal Aids for Migrant Workers in China

With the acceleration of industrialization,urbanization,as well as the reform and opening-up,the amount of migrant workers is increasing sharply. However,the specialty of criminal cases is ignored,rights of migrant farmers and legal aids for them are neglected,making them commit crimes for lack of basic knowledge of laws and failing to be treated with fairness. The aim of enjoying human rights is a failure.Based on the legal aids for migrant workers,the paper discusses how to protect legal rights of migrant workers in criminal cases and make them enjoy fairness of laws,making laws play a true part in criminal cases and fulfill the aim of human rights protection.

Somatic DNA copy number alterations and their potential clinical utility for predicting lethal prostate cancer

Current clinicopathologic indicators are insufficient to distinguish the small percentage of aggressive prostate cancer （PCa） from the vast majority of indolent disease at diagnosis, leading to overtreatment of PCa. A recent study reported and confirmed a strong association of PCa-specific mortality with somatic DNA copy number alterations （CNAs） in primary pro- state tumors.

A picture with more details is painted for prostate cancer

B y comparing all gene-coding sequences in the genome between tumors and matched normal samples from clinically localized and castration-resistant （CR） prostate cancer patients, two groups of scien- tists have recently identified more than 5000 somatic mutations.

Current approaches of genome-wide association studies

With rapid advances in high-throughput genotyping technology and the great increase in information available on SNPs throughout the genome, genome-wide association（GWA） studies have now become feasible. By testing associations of diseases or traits with a large number of SNPs that capture most of the genetic information across the genome, GWA approaches can identify variants that directly or indirectly confer risk. The systematic and objective nature of GWA increases the likelihood of identifying risk variants and may reveal novel mechanisms. The power of this approach has been empirically demonstrated by the recent success of GWA studies in many diseases,including cancers.

A Two-color Single-molecule Sequencing Platform and Its Clinical Applications

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years.In this study,we developed a single-molecule desktop sequencer,GenoCare 1600(GenoCare),which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry,making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use.Using the GenoCare platform,we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%.We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019(COVID-19)samples from throat swabs.Our findings indicate that the GenoCare platform allows for microbial quantitation,sensitive identification of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus,and accurate detection of virus mutations,as confirmed by Sanger sequencing,demonstrating its remarkable potential in clinical application.

Emerging Regulatory Mechanisms of N6-Methyladenosine Modification in Cancer Metastasis

Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and translation.Accumulating evidence demonstrates that m^(6)A plays a critical role in regulating cancer metastasis.However,there is a lack of studies that review the recent advances of m^(6)A in cancer metastasis.Here,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various cancers.Moreover,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer metastasis.This review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.

Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography

The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination （DRE） and transrectal ultrasonography （TRUS） are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen （tPSA）, free PSA, and p2PSA. For each patient, the free-to-total PSA ratio （%fPSA）, PSA density （PSAD）, p2PSA-to-free PSA ratio （%p2PSA）, and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve （AUC） and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

Phi-based risk calculators performed better in the prediction of prostate cancer in the Chinese population

Risk prediction models including the Prostate Health Index(phi)for prostate cancer have been well established and evaluated in the Western population.The aim of this study is to build phi-based risk calculators in a prostate biopsy population and evaluate their performanee in predicting prostate cancer(PCa)and high-grade PCa(Gleason score 27)in the Chinese population.We developed risk calculators based on 635 men who underwent initial prostate biopsy.Then,we validated the performance of prostate-specific antigen(PSA),phi,and the risk calculators in an additional observational cohort of 1045 men.We observed that the phi-based risk calculators(risk calculators 2 and 4)outperformed the PSA-based risk calculator for predicting PCa and high-grade PCa in the training cohort.In the validation study,the area under the receiver operating characteristic curve(AUC)for risk calculators 2 and 4 reached 0.91 and 0.92,respectively,for predicting PCa and high-grade PCa,respectively;the AUC values were better than those for risk calculator 1(PSA-based model with an AUC of 0.81 and 0.82,respectively)(all P<0.001).Such superiority was also observed in the stratified population with PSA ranging from 2.0 ng ml^-1 to 10.0 ng ml^-1.Decision curves confirmed that a considerable proportion of unnecessary biopsies could be avoided while applying phi-based risk calculators.In this study,we showed that,compared to risk calculators without phi,phi-based risk calculators exhibited superior discrimination and calibration for PCa in the Chinese biopsy population.Applying these risk calculators also considerably reduced the number of unnecessary biopsies for PCa.