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Exploring noncoding variants in genetic diseases:from detection to functional insights

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Journal of Genetics and Genomics 2024年第2期51卷 111-132页

作者： ke wu Fengxiao Bu Yang wu Gen Zhang Xin Wang Shunmin He Mo-Fang Liu Runsheng Chen Huijun Yuan Institute of Rare Diseases West China Hospital of Sichuan UniversityChengduSichuan 610041China key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China key Laboratory of RNA Biology Center for Big Data Research in HealthInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State key Laboratory of Molecular Biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

关键词： Noncoding variation Genetic disease Research approach Challenge

The circadian clock in enamel development

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International Journal of Oral Science 2024年第3期16卷 371-380页

作者： ke wu Xiaochan Li Yunyang Bai Boon Chin Heng Xuehui Zhang Xuliang Deng Department of Geriatric Dentistry Peking University School and Hospital of StomatologyBeijingChina th Division Peking University School and Hospital of StomatologyBeijingChina Department of Dental Materials&Dental Medical Devices Testing Center Peking University School and Hospital of StomatologyBeijingChina National Engineering Research Center of Oral Biomaterials and Digital Medical Devices NMPA Key Laboratory for Dental MaterialsBeijing Laboratory of Biomedical Materials&Beijing Key Laboratory of Digital StomatologyPeking University School and Hospital of StomatologyBeijingChina Oral Translational Medicine Research Center Joint Training base for Shanxi Provincial key Laboratory in Oral and Maxillofacial Repair Reconstruction and Regeneration The First People’s Hospital of Jinzhong JinzhongChina

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological *** circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external *** enamel is a type of mineralized tissue that forms the exterior surface of the tooth *** Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian *** enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during *** review will first examine the key roles of the circadian clock in regulating ameloblasts and *** physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and ***,the potential detrimental effects of circadian rhythm disruption on enamel formation are *** rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis ***,future research trajectory in this field is *** is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

关键词： enamel crown exterior

Wide Stopband Substrate Integrated Waveguide Filter Using Bisection and Trisection Coupling in Multilayer

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Chinese Journal of Electronics 2024年第2期33卷 436-442页

作者： Peng CHU Jianguo FENG Peng ZHU Lei GUO Long ZHANG Leilei LIU Guoqing LUO ke wu College of Electronic and Optical Engineering Nanjing University of Posts and Telecommunications National and Local Joint Engineering Laboratory of RF Integration and Micro-Assembly Technology School of Information and Communication Engineering Dalian University of Technology Guangdong Provincial key Laboratory of Optoelectronic Information Processing Chips and Systems Sun Yat-sen University College of Electronics and Information Engineering Shenzhen University School of Electronics and Information Hangzhou Dianzi University Poly-Grames Research Center Polytechnique Montreal

This article presents a highly efficient method for substrate-integrated-waveguide（SIW） filters to achieve very wide stopbands. By employing the proposed trisection slots in addition to the bisection slots as the inter-coupling structures, all spurious modes below TE505 of a SIW filter working in the fundamental mode TE101（f0）can be eliminated without requiring additional structure or complex theoretical analysis, without affecting the design of the fundamental passbands, and without degrading the performance of the filters. For verification, two prototype filters are designed, fabricated, and measured with wide stopbands up to 4.15f0 and 4.83f0, respectively. The proposed technique could facilitate the development of high-performance wide-stopband SIW filters for microwave/wireless circuits and systems.

关键词： Microwave measurement Couplings Filters Prototypes Nonhomogeneous media Microwave theory and techniques Microwave circuits

Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathwayin Mice

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Chinese Journal of Integrative Medicine 2024年第2期30卷 135-142页

作者： GU Li-mei LI He-zhong GAO Lei LI Hui WEI Lan-fu PAN Cheng-yu wu ke-xuan TIAN Yao-zhou Department of Gastrointestinal Endoscopy Affiliated Hospital of Nanjing University of Chinese MedicineNanjing(210029)China Department of Gastroenterology Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing(210028)China School of Integrated Chinese and Western Medicine Nanjing University of Chinese MedicineNanjing(210023)China

Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of *** 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each *** for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse *** mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent *** mRNA and protein expression levels of Nrf2,HO-1,and inhibitory keLCH like ECH-related protein 1(keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,***:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic *** to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(Pkeap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of

关键词： Huangqin Decoction colitis-associated carcinogenesis nuclear factor erythroid 2 related-factor 2/heme oxygenase signaling pathway oxidative stress Chinese medicine

Frequency-Diversified Space-Efficient Radiating Surface Using Convolved Electric and Magnetic Currents for Highly Dense Multiband Antenna-Frontend Integration

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Electromagnetic Science 2024年第1期2卷 63-76页

作者： Amirhossein Askarian Pascal Burasa ke wu Department of Electrical Engineering Poly-Grames Research CenterPolytechnique MontrealQC H3T1J4Canada

We propose and investigate a methodology based on convolved electric and magnetic currents for the generation of multi-band responses over a space-shared radiating ***,a single wideband antenna operation principle based on inter-leaved dipole and slot modes is studied and analyzed using full-wave simulations followed by a qualitative time domain ***,a 2×2 dual-band radiating unit is conceived and developed by closely arranging single wideband *** this case,multimode resonances are generated in a lower frequency band by a proper convolving and coupling of the magnetic and electric currents realized in the gaps between the antennas and on the surface of the antennas,*** methodology can be deployed repeatedly to build up a self-scalable topology by reusing the electromagnetically(EM)connected radiating surfaces and gaps be-tween the radiating *** to the efficient reuse of the electromagnetic region for the development of multiband radiation,a high aperture-reuse efficiency is ***,as a proof of concept,a 2×4 dual-band array operating in Ku-and Ka-bands is devel-oped and fabricated by a linear arrangement of the two developed radiating *** measurement results show that the proposed antenna array provides impedance and gain bandwidths of 30%and 25.4%in the Ku-band and 10.65%and 8.52%in the Ka-band,respectively.

关键词： Aperture-shared array Aperture-reused efficiency Antenna-frontend integration Dual-band antenna Magneto-electric dipole antenna Multi-mode resonance Multi-band array Multi-functional antenna Wideband antenna array

Individual virome analysis reveals the general co-infection of mammal-associated viruses with SARS-related coronaviruses in bats

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Virologica Sinica 2024年第4期39卷 565-573页

作者： Hao-Rui Si ke wu Jia Su Tian-Yi Dong Yan Zhu Bei Li Ying Chen Yang Li Zheng-Li Shi Peng Zhou wuhan Institute of Virology Chinese Academy of SciencesWuhan 43000China Guangzhou National Laboratory Guangzhou International Bio IslandGuangzhou 510005China University of Chinese Academy of Sciences Beijing 100000China State key Laboratory of Respiratory Disease The First Affiliated Hospital of Guangzhou Medical SchoolGuangzhou 510005China

Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic ***,it is conceivable that an individual bat may harbor multiple ***,there is limited knowledge on the overall co-circulation of microorganisms in ***,we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative *** these,76 individual samples were selected for further metagenomics *** found a complex microenvironment characterized by the general cocirculation of microbes from two different sources:mammal-associated viruses or environment-associated *** later includes commensal bacteria,enterobacteria-related phages,and insect or fungal viruses of food *** showed that 25%(19/76)of the samples contained at least one another mammal-associated virus,notably alphacoronaviruses(13/76)such as AlphaCoV/YN2012,HKU2-related CoV and AlphaCoV/Rf-HuB2013,along with viruses from other ***,we observed three viruses co-circulating within a single bat,comprising two coronavirus species and one *** analysis also revealed the potential presence of pathogenic bacteria or fungi in ***,we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples,some of which formed new evolutionary ***,our study reveals the complex microenvironment of bat microbiome,facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.

关键词： Bat Microbiome SARS-related coronavirus Co-infection Alphacoronavirus

中国居民消费结构转型驱动力:收入效应还是相对价格效应

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经济理论与经济管理 2024年第2期44卷 31-48页

作者：于泽吴珂中国人民大学经济学院 100872

本文基于结构转型框架,以居民消费在各部门的分配份额度量居民消费结构转型,利用1992—2017年中国居民消费支出及投入产出表等数据,通过对偏好进行非线性估计并结合反事实分析方法,实证探讨了我国居民消费结构升级的主导驱动力。研究发... 详细信息

本文基于结构转型框架,以居民消费在各部门的分配份额度量居民消费结构转型,利用1992—2017年中国居民消费支出及投入产出表等数据,通过对偏好进行非线性估计并结合反事实分析方法,实证探讨了我国居民消费结构升级的主导驱动力。研究发现:消费的不同定义和测度方式会使结论出现差异。在最终消费支出定义下,收入效应是驱动我国居民消费结构升级的主导力量;在消费增加值定义下,若利用支出法GDP方法构造消费,则相对价格效应对2002年之后我国居民消费结构升级的贡献大大增强。本文在理论层面为结构转型相关研究提供了需求侧视角,在应用层面有助于明确我国居民消费结构升级的主要动力,进而为高质量发展阶段下消费提质升级提供有益的借鉴及参考。

关键词：居民消费结构转型收入效应相对价格效应

Preoperative serum cortisone levels are associated with cognition in preschool‑aged children with tetralogy of Fallot after corrective surgery:new evidence from human populations and mice

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World Journal of Pediatrics 2024年第2期20卷 173-184页

作者： Si-Yu Ma Yu-Ting Liu Yue-Shuang Cun Qiang Wang Ming-Cui Fu ke-De wu Xin-Yu Cai Shu-Ting Cheng Nishant Patel Min Da Liang Hu Zhuoga Deqin Xue-Jun Kang Ming Yang Xu-Ming Mo Department of Cardiothoracic Surgery Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Department of Radiology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China key Laboratory of Child Development and Learning Science Research Center For Learning ScienceSchool of Biological Sciences&Medical EngineeringMinistry of EducationSoutheast UniversityNanjing 210096China Medical School of Nanjing University Nanjing 210093China

Background Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart *** with TOF would be confronted with neurological impairment across their *** study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with *** We used mass spectrometry(MS)technology to assess the levels of serum metabolites,Wechsler preschool and primary scale of intelligence-Fourth edition(WPPSI-Ⅳ)index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging(MRI)to detect cortical morphological *** Multiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal ***,preoperative SpO_(2) was negatively correlated with levels of serum cortisone after adjusting for all ***,after intervening levels of cortisone in chronic hypoxic model mice,total brain volumes were reduced at both postnatal(P)11.5 and P30 *** Our results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with *** study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

关键词： Cognition Cortisone MRI Neurodevelopment Tetralogy of Fallot

带p-Laplacian算子的分数阶微分方程半正系统正解的存在性

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东北师大学报（自然科学版） 2024年第1期56卷 29-39页

作者：杨可丽吴克晴江西理工大学理学院江西赣州341000

对一类带有p-Laplacian算子和含有分数阶积分的奇异非线性项的Riemann-Liouville型分数阶微分方程半正系统正解的存在性进行了分析与研究,其边界条件包括不同阶的分数阶导数、Riemann-Stieltjes积分和无穷点边值条件.基于相关Green函数... 详细信息

对一类带有p-Laplacian算子和含有分数阶积分的奇异非线性项的Riemann-Liouville型分数阶微分方程半正系统正解的存在性进行了分析与研究,其边界条件包括不同阶的分数阶导数、Riemann-Stieltjes积分和无穷点边值条件.基于相关Green函数的性质以及不动点指数定理,得到了参数属于合适区间时,该系统至少存在一个正解的充分条件.通过具体实例验证了所得结果的实用性.

关键词： p-Laplacian算子 Riemann-Liouville分数阶微分系统半正系统正解

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